Veelbelovende nieuwe neuroimaging
technieken voor vroegtijdige ontdekking van Alzheimer
Onderzoekers van het "International
Centre of Biomedicine" en de Universiteit van Chili, hebben, in samenwerking met het
Centrum voor Bioinformatica op de Universiteit van Talca, ontdekt dat twee medicijnen, het
benzimidazole derivaat lanzoprazole en astemizole, mogelijk geschikt zijn voor gebruik als
PET (positieve elektron afgifte tomografie) opsporing. Hierdoor wordt zichtbaarheid
mogelijk gemaakt, zodat Alzheimer in een vroeg stadium kan worden opgespoord.
De studie is gepubliceerd in de meest
recente uitgave van de "Journal of Alzheimer's Disease. Lanzoprazole en astemizole
hechten zich vooral aan pathologische oligomeren van tau, die de kern van de
neurofibrillary tangles (NFT) vormen. NFT's zijn typerende hersenbeschadigingen bij
patiënten met de ziekte van Alzheimer. De auteurs van de studie; Prof. Dr. R.B. Maccioni
en Dr. Leonel Rojo, "Aangezien de relatie tussen neurofibrillary tangles en
hersenbeschadiging bevestigd is, gaan we ervan uit dat deze geneesmiddelen een grote
potentie hebben voor (in vivo) vroegtijdige opsporing van Alzheimer en de beperking van
vorming van NFT's.
Deze studies, gebaseerd op geavanceerde
proteomics en databases van moleculaire interacties, kunnen helpen nieuwe medicijnen te
vinden om Alzheimer in een vroeg stadium op te sporen. De bevindingen zijn het resultaat
van een reeds lang gevestigd onderzoeksprogramma, gesteund door
de Alzheimer´s Association-USA en Fondecyt, Chile, om nieuwe mogelijke medicijnen te
evalueren." Technologische toepassingen van deze ontdekking worden ontwikkeld in
samenwerking met Venturel@b van de Adolfo Ibanez Universiteit.
Interessant genoeg binden lanzoprazole en
astemizole, al eerder goedgekeurd voor behandeling van proton pomp aandoeningen en
respectievelijk als antihistamine, zich ook direct aan opgehoopte varianten van het tau
eiwit; in paren lopende, spiraalvormige fijne draden (PHF's) en NFTs in door
Alzheimer aangetaste hersenen. Tot op heden was het niet mogelijk om deze pathologische
hersenstructuren in levende Alzheimer patiënten op te sporen. De enige bevestiging van de
ziekte werd verkregen door postmortale neuropathologische evaluatie. : Link
Uitleg bij de tekst: Tangles zijn
onoplosbare, gedraaide vezels, die voorkomen in de cellen van de hersenen. Deze klitten
bestaan voornamelijk uit het eiwit tau. Dit eiwit vormt een bepaalde structuur, de
zogenaamde microtubuli. De microtubule helpt voedingsstoffen en andere belangrijke stoffen
te vervoeren uit een deel van de zenuwcel naar het andere deel. Bij de ziekte van
Alzheimer, is echter het tau-eiwit abnormaal vervormd, waardoor de microtubule structuren
instorten.
Neuronen uit huidcellen bieden
nieuwe hoop voor Alzheimerpatiënten
Amerikaanse wetenschappers hebben voor de
eerste keer uit huidcellen neuronen gemaakt, schrijft the Sunday Times.
There is now available on www.YouTube.com a
six part series of interviews about ketones, coconut oil and MCT oil and the potential
benefits for people with Alzheimer's, Parkinson's and other neurodegenerative diseases.
The primary purpose of making these videos is to increase awareness of the need for
funding for large scale production of the ketone ester made by Dr. Richard Veech at the
NIH. My secondary goal is to let people know that the medium chain triglycerides in
coconut oil and MCT oil can produce circulating ketones that can act as an alternative
fuel for brain and other cells that
are insulin resistant and cannot use glucose as a fuel; the levels are considerably lower
than those that can be achieved with Dr. Veech's ketone ester, however, some improvement
or stabilization of disease may still be possible with the oils.
• Caregiver discussions about coconut
oil, MCT oil and Axona can be found at http://alzheimers.infopop.cc/eve. (For a key word
search, click on the purple "Find'' button at the top of the list.)
A U.S. researcher suggests his "myelin
model" -- based on a sheath that covers nerve axons -- is cause for rethinking
Alzheimer's disease.
Diagnose van de ziekte Alzheimer
met biomarkers is betrouwbaar
Een van de meest veel belovende methoden
voor een vroege diagnose van de ziekte van Alzheimer is het meten van specifieke eiwitten
(biomarkers) in hersenvocht. Uit een lange-termijn onderzoek van VUmc blijkt dat de meest
gebruikte biomarkers, amyloid beta en tau, inderdaad betrouwbare informatie opleveren bij
het stellen van de diagnose ziekte van Alzheimer. Voorwaarde is wel dat ervaren
laboratoria de metingen uitvoeren. De basis voor onderzoek naar een zo vroeg mogelijke
diagnose voor deze ziekte is hiermee verstevigd. Cees Mulder promoveerde op het onderzoek
'biomarkers voor de ziekte van Alzheimer' op 11 november bij VU medisch centrum. De
officiële diagnose 'Ziekte van Alzheimer' kan pas laat in het ziekte proces worden
vastgesteld. Te laat om de ontwikkeling van de ziekte te volgen, eventuele behandelingen
te ontwikkelingen en deze toe te passen. Onderzoek naar methoden om de diagnose tijdens
het leven in een zo vroeg mogelijk stadium te kunnen stellen, is essentieel om een
behandeling te vinden voor deze ziekte. Mulder onderzocht verschillende aspecten van de
meting van biomarkers, zoals de opslag van afgenomen hersenvocht en de gebruikte
meetmethoden voor het bepalen van de concentraties. De promotie van Mulder (64) is de
kroon op zijn werk bij VU medisch centrum. Mulder is sinds 1971 werkzaam bij de
organisatie en werkt sinds het begin bij de afdeling klinische chemie onder leiding van
prof. dr. M.A. Blankenstein.
Eerste stap naar Alzheimer bij
kinderen is gezet.
Studies tonen al aan dat neuronen van
Alzheimers er net zo uitzien als die van kinderen of depressieven onder stimulantia
behandeling. Maar die studies blijven verborgen.
Nieuwe aanknopingspunten voor
onderzoek Parkinson en Alzheimer
Veel ziekten van het centrale zenuwstelsel
gaan gepaard met ophoping van eiwit in de hersenen. Door de genen op te sporen die hierbij
betrokken zijn hopen onderzoekers dit proces te kunnen beïnvloeden. Het promotieonderzoek
van Tjakko van Ham lijkt interessante nieuwe aanknopingspunten te bieden voor nader
onderzoek naar verouderingsziekten. Het leverde een model op voor de ziekte van Parkinson.
Ook vond hij in een modelorganisme genen die inzicht geven in de moleculaire oorzaak van
de ziekte. De onderzoeksresultaten zijn voorgelegd aan een internationaal
wetenschappelijk tijdschrift.
Hoe het ziekenhuis 'omgaat' met
Alzheimerpatiënt
Fragment uit het VTM-nieuws van 31 augustus
2009: 62 jarige Alzheimerpatiënt verdwaalt 3 dagen in het Jan Palfijn ziekenhuis te Gent.
The Alzheimer's Project: Momentum
in Science
Copper Damages Protein that Defends
Against Alzheimer’s
Copper can damage a molecule that escorts out of the brain a substance called amyloid beta
that builds up in toxic quantities in the brains of people with Alzheimer’s disease.
The new findings demonstrate one way in which copper might contribute to the development
of the disease, though scientists say much more research needs to be done to clarify what
role, if any, copper ultimately plays.
Depression is a risk factor rather
than early sign of Alzheimer's disease
A new study by researchers at Rush University Medical Center supports the idea that
depression is truly a risk factor for Alzheimer's disease rather than a subtle early sign
of its underlying pathology. The study, published in the April issue of the Archives of
General Psychiatry, found no evidence of an increase in depressive symptoms during the
prodromal phase before the clinical diagnosis of Alzheimer's disease.
Hormone shows promise in reversing
Alzheimer's disease and stroke
Saint Louis University researchers have identified a novel way of getting a potential
treatment for Alzheimer's disease and stroke into the brain where it can do its work.
"We found a unique approach for delivering drugs to the brain," says William A.
Banks, M.D., professor of geriatrics and pharmacological and physiological science at
Saint Louis University. "We're turning off the guardian that's keeping the drugs out
of the brain." The brain is protected by the blood-brain barrier (BBB), a
gate-keeping system of cells that lets in nutrients and keeps out foreign substances. The
blood-brain barrier passes no judgment on which foreign substances are trying to get into
the brain to treat diseases and which are trying to do harm, so it blocks them without
discrimination. "The problem in treating a lot of diseases of the central nervous
system – such as Alzheimer's disease, HIV and stroke – is that we can't get
drugs past the blood-brain barrier and into the brain," says Banks, who also is a
staff physician at Veterans Affairs Medical Center in St. Louis. "Our new research
shows a way of getting a promising treatment for these types of devastating diseases to
where they need to be to work." The therapy – known as PACAP27 -- is a hormone
produced by the body that is a general neuro-protectant. PACAP stands for pituitary
adenylate cyclase-activating polypeptide. "It is a general protector of the brain
against many types of insult and injury," Banks says. He compares a specific guarding
mechanism in the BBB -- efflux pumps – to bouncers at exclusive nightclubs. While
they welcome those on the approved guest list, they look for trouble-makers trying to
crash the party, refuse to let them in and evict them if they do get in.
Author Pratchett blames his
Alzheimer's on mercury fillings
Terry Pratchett has reopened the controversy about the safety of mercury-based tooth
fillings by blaming them for his Alzheimer's disease. The author of the Discworld series
describes the fillings - which millions of Britons have - as "toxic waste".
Researchers have identified a key mechanism by which the protein sludge that kills brain
cells accumulates in Alzheimer's disease. Their findings in mice offer clues to treating
AD and also could explain why memory centers of the brain are most affected in the
disease.
A simple balance test may predict
cognitive decline in Alzheimer's disease
A simple balance test may predict cognitive decline in Alzheimer's Disease, according to a
study published in the March 2009 issue of the Journal of Alzheimer's Disease. This study
was carried out in 16 university hospital departments of neurology, geriatrics or
psychiatry in ten cities with 686 outpatients suffering from AD. This population is
representative of the AD population seen by clinicians in daily practice. Patients were
evaluated by a geriatrician every six months for up to two years, and their degree of
cognitive impairment was measured using the Mini Mental State Examination (MMSE). At the
same time, a "one-leg balance" (OLB) test was given, where a participant was
asked to stand on one leg for as long as possible. The OLB test was reported as abnormal
when the participant was unable to stand on one leg for 5 seconds or more. Participants
with an abnormal OLB at baseline or/and during the follow-up showed significantly more
cognitive decline at 12, 18 and 24 months than the participants with a OLB test normal at
baseline and normal during the follow-up. The worst condition (having an abnormal OLB at
baseline and during the follow-up= no improvement) was associated with a mean adjusted
cognitive decline of 9.2 points. The best condition (having a normal OLB at baseline and
during the follow-up = no worsening) was associated with a mean adjusted cognitive decline
of 3.8 points.
Pittsburgh Compound B finds
Alzheimer’s-associated plaques in symptom-free older adults
In the largest study of its kind, Pittsburgh Compound B, an imaging agent that could
facilitate the early diagnosis of Alzheimer's disease, has been used to identify amyloid
deposition in the brains of clinically older adults. The findings, published in this
month's issue of the Archives of Neurology, could not only shed more light on how the
illness progresses, but also open the door to the possibility of prevention strategies,
said senior investigator William E. Klunk, M.D., Ph.D., professor of psychiatry and
neurology at the University of Pittsburgh School of Medicine. He and study co-author
Chester A. Mathis, Ph.D., a Pitt professor of radiology and pharmaceutical sciences,
invented the imaging compound, dubbed PiB. It binds to certain forms of amyloid protein
plaques that are thought to destroy brain cells and have been found in the brains of
Alzheimer's disease patients. Before PiB, the deposits could only be identified during
autopsy to confirm the diagnosis in hindsight. Results of the study, which was led by
Howard J. Aizenstein, M.D., Ph.D., associate professor of psychiatry and bioengineering at
Pitt, "show that we can detect amyloid deposits before patients develop symptoms of
Alzheimer's disease," Dr. Klunk said. "That means we might have a window of
opportunity to slow or stop the process."
Anesthesia Is Found To Induce
Hyperphosphorylation of Tau at Sites Related to Alzheimer’s Disease
Scientists from The New York State Office of Mental Retardation and Developmental
Disabilities’ (OMRDD) New York State Institute for Basic Research in Developmental
Disabilities (IBR) report today in the March 2009 issue of the Journal of Alzheimer’s
Disease that anesthesia induces phosphorylation of tau. Tau is a key neuronal protein
involved in neurodegeneration in Alzheimer’s disease (AD) and several other
neurodegenerative disorders. Anesthesia has previously been found to be associated with
cognitive impairment and the risk for AD. This study helps elucidate the molecular
mechanisms underlying these associations. The researchers found that in test animals,
anesthesia for short periods (30 seconds to 5 minutes) induced tau phosphorylation at some
selective phosphorylation sites to a small but significant extent. Anesthesia for a longer
time (1 hour) induced much more dramatic phosphorylation at the same sites, possibly as a
result of anesthesia-induced hypothermia. The observation that anesthesia did not induce
global hyperphosphorylation of brain proteins, but instead specific hyperphosphorylation
of tau protein at the AD-related abnormal hyperphosphorylation sites suggests that tau
hyperphosphorylation might be the mechanism that links anesthesia and the risk of
cognitive impairment and/or AD. AD is the most common cause of dementia in adults and
affects approximately 27 million individuals worldwide and over four million in the United
States alone. Most AD cases are sporadic and are believed to be caused by multiple
factors. Understanding the mechanism by which anesthesia may increase the risk for
cognitive impairment will help in the design of strategies for preventing and treating
dementia and AD. “This is a very important finding related to Alzheimer’s
disease,” said OMRDD Commissioner Diana Jones Ritter. “I am pleased that these
findings will lead to helping people live richer lives through the research
findings.”
A virus that commonly infects potatoes bears a striking resemblance to one of the key
proteins implicated in Alzheimer's disease, and researchers have used that to develop
antibodies that may slow or prevent the onset of AD.
Common anesthetic induces
Alzheimer's-associated changes in mouse brains
For the first time researchers have shown that a commonly used anesthetic can produce
changes associated with Alzheimer's disease in the brains of living mammals, confirming
previous laboratory studies. In their Annals of Neurology report, which has received early
online release, a team of Massachusetts General Hospital (MGH) investigators shows how
administration of the gas isoflurane can lead to generation of the toxic amyloid-beta
(A-beta) protein in the brains of mice. "These are the first in vivo results
indicating that isoflurane can set off a time-dependent cascade inducing apoptosis [cell
death] and enhanced levels of the Alzheimer's-associated proteins BACE and A-beta,"
says Zhongcong Xie, MD, PhD, of the MassGeneral Institute for Neurodegenerative Disease
(MGH-MIND) and the MGH Department of Anesthesia and Critical Care, the study's lead and
corresponding author. "This work needs to be confirmed in human studies, but it's
looking like isoflurane may not be the best anesthesia to use for patients who already
have higher A-beta levels, such as the elderly and Alzheimer's patients." Alzheimer's
disease is characterized by deposition of A-beta plaques within the brain. The A-beta
protein is formed when the larger amyloid precursor protein (APP) is clipped by two
enzymes – beta-secretase, also known as BACE, and gamma-secretase – to release
the A-beta fragment. Normal processing of APP by an enzyme called alpha-secretase produces
an alternative, non-toxic protein. Several studies have suggested that surgery and general
anesthesia may increase the risk of developing Alzheimer's disease, and it is well known
that a small but significant number of surgical patients experience a transient form of
dementia in the postoperative period. Last year the MGH team showed that applying
isoflurane to cultured neural cells increased activation of the cell-death protein caspase
and raised levels of BACE and gamma-secretase as part of a pathway leading to the
generation of A-beta. The current study was designed to see if the same process takes
place in mice.
Study suggests blood test for
Alzheimer’s possible
Researchers have revealed a direct relationship between two specific antibodies and the
severity of Alzheimer’s disease symptoms, raising hopes that a diagnostic blood test
for the devastating disorder is within reach.Researchers from the University of Georgia,
the Charlie Norwood VA Medical Center in Augusta and the Medical College of Georgia
compared antibody levels in blood samples from 118 older adults with the
participant’s level of dementia. The team, whose results appear in the current
edition of Journal of Gerontology: Medical Sciences, found that the concentration of two
specific proteins that are involved in the immune response increases as the severity of
dementia increases."We found a strong and consistent relationship between two
particular antibodies and the level of impairment,” said study co-author L. Stephen
Miller, professor and director of clinical psychology training in the UGA Franklin College
of Arts and Sciences. “The finding brings us closer to our ultimate goal of
developing a blood test that can diagnose Alzheimer’s disease or potentially identify
if someone is at higher risk for the disease.”
LSUHSC research identifies key
contributor to Alzheimer's disease process
Walter J. Lukiw, PhD, Associate Professor of Neuroscience and Ophthalmology at LSU Health
Sciences Center New Orleans, is the lead author of a paper identifying, for the first
time, a specific function of a fragment of ribonucleic acid (RNA), once thought to be no
more than a byproduct, in regulating inflammation and the development of Alzheimer's
disease. The paper, An NF-kB-sensitive micro RNA-146a-mediated inflammatory circuit in
Alzheimer's disease and in stressed human brain cells, will be published in the November
14, 2008 issue of The Journal of Biological Chemistry. Dr. Lukiw's lab at the LSU Health
Sciences Center New Orleans Neuroscience Center of Excellence has shown that this tiny
piece of RNA, or microRNA, called miRNA-146a is found in increased amounts in stressed
human brain cells and in Alzheimer's disease, and that it plays a crucial role in the
regulation of inflammation and disease-related neuropathology thought to be integral to
the Alzheimer's disease process. Dr. Lukiw's research team, which also included LSUHSC's
Jian Guo Cui, MD, PhD and Yuhai Zhao, a post doctoral student in the lab, demonstrated in
human brain cells in primary culture that MiRNA-146a targets the messenger RNA of an
important anti-inflammatory regulator called complement factor H (CFH). Testing both
control cells and Alzheimer's disease-affected tissues, they found that miRNA-164a appears
to reduce the amount and bioavailability of CFH, promoting the inflammation of brain cells
and contributing to the development of Alzheimer's disease.
Brain damage found in cognitively
normal people with Alzheimer's marker
Researchers at Washington University School of Medicine in St. Louis have linked a
potential indicator of Alzheimer's disease to brain damage in humans with no signs of
mental impairment. Although their cognitive and neurological assessments were normal,
study participants with lower levels of a substance known as amyloid beta 42 (A-beta 42)
in their cerebrospinal fluid (CSF) had reduced whole brain volumes, suggesting that
Alzheimer's changes might already be damaging their brains. Scientists previously showed
that low CSF levels of A-beta 42 mark the presence of amyloid deposition in the brain, a
key diagnostic marker of the amyloid plaques that characterize Alzheimer's disease.
Evidence is mounting that Alzheimer's harms the brain for many years before physicians and
family members can detect symptoms, and this has led many to conclude that successful
Alzheimer's treatments may only be possible if scientists find ways to identify
pre-symptomatic sufferers. The results are an encouraging sign that this search for new
indicators, known as antecedent biomarkers, may be succeeding, according to senior author
David M. Holtzman, M.D., the Andrew and Gretchen Jones Professor and chair of the
Department of Neurology at the School of Medicine and neurologist-in-chief at
Barnes-Jewish Hospital. "We still need to confirm with long-term follow-up studies
that subjects with this biomarker and brain damage go on to develop the cognitive changes
characteristic of Alzheimer's," says Holtzman. "For now, the evidence we've
uncovered further proves that identification and treatment prior to the start of the
symptoms of Alzheimer's disease are likely going to be essential to preventing
irreversible brain injury."
Vitamin E May Help Alzheimer’s
Patients Live Longer
People with Alzheimer's disease who take vitamin E appear to live longer than those who
don't take vitamin E, according to research that will be presented at the American Academy
of Neurology 60th Anniversary Annual Meeting in Chicago, April 12–19, 2008. For the
study, researchers followed 847 people with Alzheimer's disease for an average of five
years. About two-thirds of the group took 1,000 international units of vitamin E twice a
day along with an Alzheimer’s drug (a cholinesterase inhibitor). Less than 10 percent
of the group took vitamin E alone and approximately 15 percent did not take vitamin E. The
study found people who took vitamin E, with or without a cholinesterase inhibitor, were 26
percent less likely to die than people who didn't take vitamin E.
Biomarkers for Alzheimer's disease
can be trusted in clinical trials
The best-established biomarkers for Alzheimer's disease have a low natural variation over
two years. The results speak for the inclusion of these biomarkers in clinical trials of
novel drugs against Alzheimer's disease.
Alzheimer’s Starts Earlier for
Heavy Drinkers, Smokers
Heavy drinkers and heavy smokers develop Alzheimer’s disease years earlier than
people with Alzheimer’s who do not drink or smoke heavily, according to research that
will be presented at the American Academy of Neurology 60th Anniversary Annual Meeting in
Chicago, April 12–19, 2008. “These results are significant because it’s
possible that if we can reduce or eliminate heavy smoking and drinking, we could
substantially delay the onset of Alzheimer’s disease for people and reduce the number
of people who have Alzheimer’s at any point in time,” said study author Ranjan
Duara, MD, of the Wien Center for Alzheimer’s Disease at Mount Sinai Medical Center
in Miami Beach, FL, and Fellow of the American Academy of Neurology.
Children's Hospital Oakland
scientist finds potential Alzheimer's cure in century-old drug
A new study conducted by researchers at Children's Hospital & Research Center Oakland
shows that a century-old drug, methylene blue, may be able to slow or even cure
Alzheimer's and Parkinson's disease. Used at a very low concentration – about the
equivalent of a few raindrops in four Olympic-sized swimming pools of water - the drug
slows cellular aging and enhances mitochondrial function, potentially allowing those with
the diseases to live longer, healthier lives. A paper on the methylene blue study,
conducted by Hani Atamna, PhD, and a his team at Children's, was published in the March
2008 issue of the Federation of American Societies for Experimental Biology (FASEB)
Journal. Dr. Atamna's research found that methylene blue can prevent or slow the decline
of mitochondrial function, specifically an important enzyme called complex IV. Because
mitochondria are the principal suppliers of energy to all animal and human cells, their
healthy function is critical. "The results are very encouraging," said Dr.
Atamna. "We'd eventually like to try to prevent the physical and cognitive decline
associated with aging, with a focus on people with Alzheimer's disease. One of the key
aspects of Alzheimer's disease is mitochondrial dysfunction, specifically complex IV
dysfunction, which methylene blue improves. Our findings indicate that methylene blue, by
enhancing mitochondrial function, expands the mitochondrial reserve of the brain. Adequate
mitochondrial reserve is essential for preventing age-related disorders such as
Alzheimer's disease."
Another McGill/JGH breakthrough
opens door to early Alzheimer's diagnosis
A new diagnostic technique which may greatly simplify the detection of Alzheimer's disease
has been discovered by researchers at McGill University and the affiliated Lady Davis
Institute for Medical Research at Montreal's Jewish General Hospital (JGH). Their results
were published June 8 in the Journal of Alzheimer's Disease. There is currently no
accepted blood test for Alzheimer's, and the diagnosis is usually based on expensive and
labour-intensive neurological, neuropsychological and neuroimaging evaluations. Dr. Hyman
Schipper and colleagues at the Lady Davis Institute and McGill University utilized a new
minimally-invasive technique called near-infrared (NIR) biospectroscopy to identify
changes in the blood plasma of Alzheimer's patients, changes which can be detected very
early after onset, and possibly in pre-clinical stages of the disease. Biospectroscopy is
the medical form of spectroscopy, the science of detecting the composition of substances
using light or other forms of energy. In NIR spectroscopy, different substances emit or
reflect light at specific, detectable wavelengths.
Pipex test confirms copper
involvement in Alzheimer's disease
Pipex Pharmaceuticals has announced positive clinical results of Alzheimer's disease test
that used FreeBound, Pipex's proprietary pharmacodiagnostic device for measurement of
serum free and total copper. The test demonstrated the significance of copper in
Alzheimer's disease.
A novel way found to prevent
protein plaques implicated in Alzheimer's
For unknown reasons a protein called amyloid beta aggregates into toxic plaques in the
brain, killing neurons. These plaques are one of the hallmarks of Alzheimer's disease. Now
two new animal studies show for the first time that the deadly transformation of amyloid
beta into plaques can be prevented through an interaction between amyloid beta and another
protein called cystatin C.
A new study in mice finds that plaques associated with Alzheimer’s wreak havoc on
calcium’s role in cell signaling. Careful journalists write that Alzheimer’s
disease is associated with the characteristic plaques in patients’ brains, never that
it’s caused by those plaques.
LSUHSC research reports new method
to protect brain cells from diseases like Alzheimer's
New research led by Chu Chen, PhD, Associate Professor of Neuroscience at LSU Health
Sciences Center New Orleans, provides evidence that one of the only naturally occurring
fatty acids in the brain that has the ability to interact with the receptors originally
identified as the targets of THC (the psychoactive component of marijuana) can help to
protect brain cells from neurodegenerative diseases like Alzheimer's and Parkinson's.
Published in the August 15, 2008 issue of the Journal of Biological Chemistry, the
research focuses on the cellular and molecular mechanisms of inflammation, specifically
the role these relatively recently discovered endogenous cannabinoids can play in the
control of COX-2 and other cyclooxygenases. COX-2 is a key player in neuroinflammation and
has been implicated in the development of neurodegenerative diseases and worsening of
damage from such insults as traumatic brain injury and stroke.Chen and research associate
Jian Zhang show that endocannabinoid 2-arachidonoylglycerol (2-AG) functions as an
endogenous COX-2 inhibitor, turning off the production of COX-2 which normally goes into
overdrive in response to pro-inflammatory and certain types of toxic stimuli, resulting in
the injury or death of brain cells. The researchers also revealed the specific signaling
pathways that regulate the 2-AG suppression of COX-2. The paper, Endocannabinoid
2-Arachidonoylglycerol Protects Neurons by Limiting COX-2 Elevation, is available online
at http://www.jbc.org.
Brain damage found in cognitively
normal people with Alzheimer's marker
Researchers at Washington University School of Medicine in St. Louis have linked a
potential indicator of Alzheimer's disease to brain damage in humans with no signs of
mental impairment. Although their cognitive and neurological assessments were normal,
study participants with lower levels of a substance known as amyloid beta 42 (A-beta 42)
in their cerebrospinal fluid (CSF) had reduced whole brain volumes, suggesting that
Alzheimer's changes might already be damaging their brains. Scientists previously showed
that low CSF levels of A-beta 42 mark the presence of amyloid deposition in the brain, a
key diagnostic marker of the amyloid plaques that characterize Alzheimer's disease.
Evidence is mounting that Alzheimer's harms the brain for many years before physicians and
family members can detect symptoms, and this has led many to conclude that successful
Alzheimer's treatments may only be possible if scientists find ways to identify
pre-symptomatic sufferers.
In studies of human brain cells, the widely-used anesthetic desflurane does not contribute
to increased production of amyloid-beta protein; however, when combined with low oxygen
conditions, it can produce more of this Alzheimer's associated protein.
Compounds Have Potential For
Diagnosis, Treatment Of Alzheimer's Disease
Scientists have discovered that these compounds interact in three specific ways with the
tau protein, which is the subject of a growing body of research into the causes and
progression of dementia.In a normal, healthy brain, the tau protein binds to and
stabilizes structures in the brain that are essential for proper functioning. But tau
protein that breaks away from these structures can begin forming long strands called
filaments. These filaments can clump into tangles, which are a marker of Alzheimer’s
disease and other neurodegenerative disorders. Depending on the specific compounds under
study, they can produce three different outcomes when introduced to the tau protein: They
either bind to the protein filaments; inhibit the filaments from developing; or drive tau
protein to form filaments. So far, the interactions have been observed in test tubes and
cell cultures, so any clinical use of the compounds will require years of additional
research.
Coatings To Help Medical Implants
Connect With Neurons
Plastic coatings could someday help neural implants treat conditions as diverse as
Parkinson's disease and macular degeneration. The coatings encourage neurons in the body
to grow and connect with the electrodes that provide treatment. Jessica O. Winter,
assistant professor of chemical and biomolecular engineering at Ohio State University
described the research Thursday, August 21 at the American Chemical Society meeting in
Philadelphia. She is also an assistant professor of biomedical engineering. Worldwide,
researchers are developing medical implants that stimulate neurons to treat conditions
caused by neural damage. Most research focuses on preventing the body from rejecting the
implant, but the Ohio State researchers are focusing instead on how to boost the implants'
effectiveness.
Alzheimer's Disease Neuroimaging
Initiative announces completion of genome-wide analysis
Researchers announced today that a high-density genome wide analysis of participants in
the Alzheimer's Disease Neuroimaging Initiative (ADNI; www.adni-info.org) is more than 95%
complete and that data will be shared with scientists around the world for further
analysis. The ADNI data will be used by researchers to search for genes that contribute to
the development of Alzheimer's disease, which currently affects up to 5 million people in
the United States alone. ADNI, an ongoing $60 million project, is a public-private
partnership supported primarily by the National Institutes of Health (NIH) with
pharmaceutical and related industries and not-for-profit organizations providing support
through the Foundation for the National Institutes of Health (FNIH). One of the largest
scale neuroimaging projects ever undertaken, ADNI involves longitudinal magnetic resonance
imaging (MRI) and positron emission tomography (PET) brain imaging and blood, urine and
spinal fluid biomarker studies of more than 800 individuals, half of whom have mild
cognitive impairment, a condition placing them at high risk for developing Alzheimer's
disease or another dementia. The primary goal of ADNI is to determine whether brain
imaging, other biological markers, and clinical and neuropsychological assessment can
accurately measure the progression of mild cognitive impairment and early Alzheimer's
disease. The identification of specific biomarkers of early Alzheimer's disease and
disease progression will provide a useful tool for researchers and clinicians in both the
diagnosis of early Alzheimer's disease and in the development, assessment and monitoring
of new treatments. One major Alzheimer's disease risk gene, APOE, has been consistently
shown to be associated with the form of the disease arising later in life that accounts
for approximately 95 percent of all cases. It is widely suspected that variants in an
ensemble of other genes play a role in susceptibility to the disease and may influence the
age of onset, expression and rate of progression of neurodegenerative changes in the
brain. "This new data set provides a unique opportunity to evaluate the associations
between a highly comprehensive dataset based on brain imaging, clinical examinations and
other biomarkers and the entire genome or selected candidate genes," said Andrew
Saykin, Psy.D., director of the IU Center for Neuroimaging at the Indiana University
School of Medicine, who leads the genetics research team.
Novel approach to treat Alzheimer's
and other diseases offered by targeting cell membrane RAFTS
This week in Science magazine, researchers from JADO Technologies, with colleagues at the
Max Planck Institute and others, report on a potential new strategy for targeting
Alzheimer's by inhibiting ß-secretase, the enzyme involved in plague formation. This new
strategy hitchhikes onto a natural cellular mechanism called RAFT that allows a
ß-secretase inhibitor to be anchored via a proprietary sterol linker into endosomes, the
precise location where ß-secretase is most active and exerts its neurotoxic activity.
A variant of the gene CDC2 could possibly be used as a risk marker for Alzheimer's
disease. The gene variant is considerably more common among Alzheimer's patients. This is
shown in a dissertation from the Sahlgrenska Academy at Göteborg University in Sweden.
Alzheimer's disease has several different causes. Since many patients have a close
relative who also developed the disease, heredity is believed to be one of the most
important factors.
Study Confirms Validity of
Pittsburgh Compound-B in Identifying the Toxins Associated with Alzheimer’s Disease
A groundbreaking study conducted by University of Pittsburgh Alzheimer’s disease
researchers reported in the journal Brain (currently online) confirms that Pittsburgh
Compound-B (PiB) binds to the telltale beta-amyloid deposits found in the brains of
patients with Alzheimer’s disease. The finding is a significant step toward enabling
clinicians to provide a definitive diagnosis of Alzheimer’s disease in living
patients.
Automated analysis of MR images may
identify early Alzheimer’s disease
Analyzing MRI studies of the brain with software developed at the Martinos Center for
Biomedical Imaging at Massachusetts General Hospital (MGH) may allow diagnosis of
Alzheimer's disease and of mild cognitive impairment, a lesser form of dementia that
precedes the development of Alzheimer's by several years. In their report that will appear
in the journal Brain and has been released online, the MGH/Martinos team show how their
software program can accurately differentiate patients with mild cognitive impairment or
Alzheimer's disease from normal elderly individuals based on anatomic differences in brain
structures known to be affected by the disease. "Traditionally Alzheimer's has been
diagnosed based on a combination of factors – such as a neurologic exam, detailed
medical history and written tests of cognitive functioning – with neuroimaging used
primarily to rule out other diseases such as stroke or a brain tumor," says Rahul
Desikan MD, PhD, of the Martinos Center and Boston University School of Medicine, lead
author of the Brain paper. "Our findings show the feasibility and importance of using
automated, MRI-based neuroanatomic measures as a diagnostic marker for Alzheimer's
disease." The researchers note that mild cognitive impairment occurs in about 20
percent of elderly individuals – as many as 40 percent of those over 85 – 80
percent of whom develop Alzheimer's within five or six years. Since drugs that may slow
the progression of Alzheimer's are in development, the ability to treat patients in the
earliest stages of the disease may significantly delay progression to dementia. To
investigate whether MR imaging can produce diagnostic markers for mild cognitive
impairment and Alzheimer's disease, the research team used FreeSurfer – an openly
available imaging software package developed at the Martinos Center and the University of
California at San Diego – to examine a number of neuroanatomic regions across a range
of normal individuals and patients with mild cognitive impairment and Alzheimer's disease.
Cerebrospinal fluid shows
Alzheimer¿s disease deterioration much earlier
It is possible to determine which patients run a high risk of developing Alzheimer’s
disease and the dementia associated with it, even in patients with minimal memory
impairment. This has been shown by recent research at the Sahlgrenska Academy.The results
have been published in the most recent issue of the prestigious medical journal Lancet
Neurology. "The earlier we can catch Alzheimer’s disease, the more we can do for
the patient. The disease is one that progresses slowly, and the pharmaceuticals that are
currently available are only able to alleviate the symptoms", says Kaj Blennow,
professor at the Sahlgrenska Academy, and a world?leading researcher in the field.
Mechanism of Alzheimer's suggests
combination therapy needed
Researchers at the University of Illinois at Chicago College of Medicine have discovered a
mode of action for mysterious but diagnostic protein snarls found in the brains of
Alzheimer's patients that suggests a one-two punch of therapy may be needed to combat the
neurodegenerative disease. Alzheimer's disease, which may affect as many as 5 million
Americans and is among the most costly diseases to society in the United States and
Europe, is characterized by two distinctive protein malformations: amyloid plaques and tau
tangles. Amyloid plaques are sticky deposits made up of a short protein called amyloid
beta, and tau tangles are made of short filaments of the tau protein. So far no one has
been able to explain how amyloid beta and the tau tangles wreak their damage on the
nervous system. "We have known for a long time that amyloid beta was bad," said
Scott Brady, professor and head of anatomy and cell biology at the UIC College of
Medicine. "What we haven't understood is why it's bad." The findings, reported
in a new study appearing in the Proceedings of the National Academy of Sciences Online
Early Edition for March 16-20, suggest promising new targets for combination therapy. In
previous work, published earlier this year, the researchers suggested how tau tangles work
together with amyloid beta to create a perfect storm that destroys neural function and
memory. "Cell death occurs at a very late stage of the disease," said Brady,
principal investigator of the study. "Long before the cells die they lose function,
and that function is critical for the symptoms that we see." Brady and his colleagues
found that when short assemblies of amyloid -- rather than the long-chain plaques -- get
inside neurons, they interfere with the cells' transport system. This limits their ability
to send vital proteins and vesicles to where they are needed within the cell and
interferes with the synaptic connections to other nerve cells.
Low level of conscientiousness may
be a risk factor for Alzheimer's disease
Individuals who are more conscientious -- in other words, those with a tendency to be
self-disciplined, scrupulous and purposeful -- appear less likely to develop Alzheimer's
disease, according to a report in the October issue of Archives of General Psychiatry, one
of the JAMA/Archives journals.
New project uses nanoparticles to
tackle Alzheimer's disease
A new EU-funded project is exploring the use of nanoparticles in the diagnosis and
treatment of Alzheimer's disease. The five-year NAD ('Nanoparticles for the therapy and
diagnosis of Alzheimer's disease') initiative has a budget of €14.6 million and is
financed by the EU's Seventh Framework Programme (FP7). It brings together researchers
from a variety of disciplines working in 19 organisations in 13 countries. The NAD project
will design a range of nanoparticles that are able to cross the blood-brain barrier to get
to the main site of the disease. Attached to these nanoparticles will be molecules that
are able to recognise and destroy the amyloid plaques. Initial studies will be carried out
on transgenic mice; if these prove successful, tests will be carried out on human
subjects.
Diabetic individuals have a significantly higher risk of developing Alzheimer's disease
but the molecular connection between the two remains unexplained. Now, researchers at the
Salk Institute for Biological Studies identified the probable molecular basis for the
diabetes -- Alzheimer's interaction.
Researchers Seeking to Identify
Alzheimer’s Risk with New Biomarkers Make Significant Progress by Focusing on a
Specific Blood Marker
A simple blood test to detect whether a person might develop Alzheimer’s disease is
within sight and could eventually help scientists in their quest toward reversing the
disease’s onset in those likely to develop the debilitating neurological condition,
Columbia University Medical Center researchers announced today. Building on a study that
started 20 years ago with an elderly population in Northern Manhattan at risk or in
various stages of developing Alzheimer’s disease, the Columbia research group has
yielded ground-breaking findings that could change the way the disease is treated or
someday prevent it. These findings suggest that by looking at the blood doctors may be
able to detect a person’s predisposition to developing the dementia-inducing disease
that robs a person of their memory and ability carry out tasks essential to life.
Alzheimer's discovery could bring
early diagnosis, treatment closer
A discovery made by researchers at McGill University and the affiliated Lady Davis
Research Institute for Medical Research at Montreal's Jewish General Hospital offers new
hope for the early diagnosis and treatment of Alzheimer's disease. In a study published in
the Journal of Biological Chemistry on May 15, Dr. Hemant Paudel, his PhD student Dong Han
and postdoctoral fellows Hamid Qureshi and Yifan Lu, report that the addition of a single
phosphate to an amino acid in a key brain protein is a principal cause of Alzheimer's.
Identifying this phosphate, one of up to two-dozen such molecules, could make earlier
diagnosis of Alzheimer's possible and might, in the longer term, lead to the development
of drugs to block its onset. The crucial protein, called a tau protein, is a normal part
of the brain and central nervous system. But in Alzheimer's patients, tau proteins go out
of control and form tangles that, along with senile plaques, are the primary cause of the
degenerative disease. Several years ago, it was discovered that tau proteins in normal
brains contain only three to four attached phosphates, while abnormal tau in Alzheimer's
patients have anywhere from 21 to 25 additional phosphates. Paudel and his team have
discovered that it is the addition of a single phosphate to the Ser202 amino acid within
the tau brain protein that is the principal culprit responsible for Alzheimer's. "The
impact of this study is twofold," said Paudel, associate professor at McGill's Dept.
of Neurology and Neurosurgery, and Project Director at the Bloomfield Centre for Research
in Aging at the Lady Davis. "We can now do brain imaging at the earliest stages of
the disease. We don't have to look for many different tau phosphates, just this single
phosphate. The possibility of early diagnosis now exists. "Second, the enzyme which
puts this phosphate on the tau can be targeted by drugs, so therapies can be developed.
This discovery gives us, for the first time, a clear direction towards the early diagnosis
and treatment of Alzheimer's."
Alzheimer's Disease Could Be
Triggered by Brain Toxins
But emerging evidence indicates that toxic environmental exposures, in combination with
nutritional, social, and exercise factors, may play a major role in the development of
Alzheimer’s disease, Parkinson’s disease, and other chronic degenerative
diseases, according to Philip Landrigan, MD.
Rapid changes in key Alzheimer's
protein described in humans
For the first time, researchers have described hour-by-hour changes in the amount of
amyloid beta, a protein that is believed to play a key role in Alzheimer's disease, in the
human brain. A collaborative team of scientists at Washington University School of
Medicine in St. Louis and the University of Milan report their results this week in
Science. "Proving that we can directly measure amyloid beta in the human brain is an
important step forward for both clinical and basic research, and that may be true not just
in Alzheimer's disease but also in other serious neurological disorders," says
co-first author David L. Brody, M.D., Ph.D., a Washington University neurologist who
treats brain injury and general neurology patients at Barnes-Jewish Hospital. The results
of the study contradicted the expectations of researchers, who were hoping to learn why
brain injury is linked to higher risk of Alzheimer's disease. They had hypothesized that
such injuries, caused by motor vehicle accidents, assaults and falls, would lead to an
increase in amyloid beta levels. Instead, they found recovery from brain injury, rather
than the injury itself, seemed to increase amyloid. The better a patient's overall
neurological status, the higher their amyloid beta levels rose."We can't at this
point rule out a very early spike in amyloid right after a brain injury," notes
Brody, assistant professor of neurology. "This study is just the beginning."
Cholesterol metabolism links early-
and late-onset Alzheimer's disease
Researchers at Washington University School of Medicine in St. Louis have uncovered
evidence strengthening the case for another potential cause of Alzheimer's. The finding
also represents the first time scientists have found a connection between early- and
late-onset Alzheimer's.
Deficiencies in the levels of folate in the blood can triple a person's risk of developing
Alzheimer's and other forms of dementia, according to researchers. Folate, which is also
known as vitamin B9, is found in most dark green vegetables.
For Prof. Beka Solomon it was obvious. If it isn`t possible to send drugs to the brain to
treat Alzheimer`s disease the normal way because of the blood-brain barrier that prevents
drugs from moving from the blood stream into the brain, then send them through the nose
instead. Solomon, of the Molecular Microbiology and Biotechnology Department at Tel Aviv
University, has been working in this field for the last 13 years after years of research
in immunotherapy, and found in mouse trials that filamentous phages, a harmless bacterial
virus found almost everywhere from the depths of the ocean to the lining of the stomach,
can be an effective treatment against Alzheimer`s disease when carried to the brain
through the nose.
International TGen-led team finds
link between brain protein and Alzheimer's disease
Investigators at the Translational Genomics Research Institute (TGen) today announced a
link between the brain protein KIBRA and Alzheimer's disease, a discovery that could lead
to promising new treatments for this memory-robbing disorder. The new discovery builds on
a previous TGen-led study published in the prestigious journal Science, which showed a
genetic link between KIBRA and memory in healthy adults. In the new study, TGen
researchers found that carriers of a memory-enhancing flavor of the KIBRA gene had a 25
percent lower risk of developing Alzheimer's disease. The findings were reported Saturday
in the online edition of Neurobiology of Aging, a Philadelphia-based peer-review journal
that generally focuses on how aging affects the nervous system. "This research
suggests that KIBRA, and possibly some of the proteins with which it interacts, may play a
role in Alzheimer's disease," said Dr. Matthew Huentelman, an investigator in TGen's
Neurogenomics Division and the paper's senior author.
MBL researchers discover a
mechanism of neurodegeneration in Alzheimer's disease
Tiny, toxic protein particles severely disrupt neurotransmission and inhibit delivery of
key proteins in Alzheimer's disease, two separate studies by Marine Biological Laboratory
(MBL) researchers have found. The particles are minute clumps of amyloid beta, which has
long been known to accumulate and form plaques in the brain of Alzheimer's patients.
"These small particles that haven't aggregated into plaques—these are
increasingly being seen as the really toxic species of amyloid beta," says Scott
Brady of University of Illinois College of Medicine, who has been an MBL investigator
since 1982. Brady and his colleagues found that these particles inhibit neurons from
communicating with each other and with other target cells in the body. "The disease
symptoms for Alzheimer's are associated not with the death of the neurons – that is a
very late event – but with the loss of functional connections. It's when the neuron
is no longer talking to its targets that you start to get the memory deficits and dementia
associated with the disease," Brady says. The amyloid beta particles activate an
enzyme, CK2, which in turn disrupts the "fast axonal transport" system inside
the neuron, Brady found. This transport system has motor proteins that move various kinds
of cargo (including neurotransmitters and the associated protein machinery for their
release) from place to place in the neuron on microtubule tracks. Brady's findings are
complemented by a new study by Rudolfo Llinás of New York University School of Medicine.
Brady and Llinás both conduct neuroscience research at the MBL using the giant nerve cell
of the Woods Hole squid, Loligo paeleii, as a model system.
Cerebrospinal fluid shows
Alzheimer's disease deterioration much earlier
It is possible to determine which patients run a high risk of developing Alzheimer’s
disease and the dementia associated with it, even in patients with minimal memory
impairment. This has been shown by recent research at the Sahlgrenska Academy, University
of Gothenburg, Sweden. The results have been published in the most recent issue of the
prestigious medical journal Lancet Neurology. "The earlier we can catch
Alzheimer’s disease, the more we can do for the patient. The disease is one that
progresses slowly, and the pharmaceuticals that are currently available are only able to
alleviate the symptoms", says Kaj Blennow, professor at the Sahlgrenska Academy, and
a world?leading researcher in the field. Several biomarkers have been identified in recent
years. Biomarkers are proteins that can be detected in the cerebrospinal fluid and used to
diagnose Alzheimer’s disease. It is now clear that the typical pattern of biomarkers
known as the "CSF AD profile" can be seen in the cerebrospinal fluid of patients
even with very mild memory deficiencies, before these can be detected by other tests.
Is vitamin D deficiency linked to
Alzheimer's disease and vascular dementia?
There are several risk factors for the development of Alzheimer's disease and vascular
dementia. Based on an increasing number of studies linking these risk factors with Vitamin
D deficiency, an article in the current issue of the Journal of Alzheimer's Disease (May
2009) by William B. Grant, PhD of the Sunlight, Nutrition, and Health Research Center
(SUNARC) suggests that further investigation of possible direct or indirect linkages
between Vitamin D and these dementias is needed. Low serum levels of 25-hydroxyvitamin D
[25(OH)D] have been associated with increased risk for cardiovascular diseases, diabetes
mellitus, depression, dental caries, osteoporosis, and periodontal disease, all of which
are either considered risk factors for dementia or have preceded incidence of dementia. In
2008, a number of studies reported that those with higher serum 25(OH)D levels had greatly
reduced risk of incidence or death from cardiovascular diseases. Several studies have
correlated tooth loss with development of cognitive impairment and Alzheimer's disease or
vascular dementia. There are two primary ways that people lose teeth: dental caries and
periodontal disease. Both conditions are linked to low vitamin D levels, with induction of
human cathelicidin by 1,25-dihydroxyvitamin D being the mechanism. There is also
laboratory evidence for the role of vitamin D in neuroprotection and reducing
inflammation, and ample biological evidence to suggest an important role for vitamin D in
brain development and function.
Researchers find 1 in 6 women, 1 in
10 men at risk for Alzheimer's disease in their lifetime
Researchers from Boston University School of Medicine have estimated that one in six women
are at risk for developing Alzheimer's disease in their lifetime, while the risk for men
is one in ten. These findings were released today by the Alzheimer's Association in their
publication 2008 Alzheimer’s Disease: Facts and Figures.
New mechanism for amyloid beta
protein's toxic impact on the Alzheimer's brain
Scientists have uncovered a novel mechanism linking soluble amyloid ? protein with the
synaptic injury and memory loss associated with Alzheimer's disease (AD). The research,
published by Cell Press in the June 25 issue of the journal Neuron, provides critical new
insight into disease pathogenesis and reveals signaling molecules that may serve as
potential additional therapeutic targets for AD. Amyloid ? protein (A?) plays a major
pathogenic role in AD, a devastating neurodegenerative disorder characterized by
progressive cognitive impairment and memory loss. "Given the mounting evidence that
small soluble A? assemblies mediate synaptic impairment in AD, elucidating the precise
molecular pathways by which this occurs has important implications for treating and
preventing the disease," explains senior study author, Dr. Dennis Selkoe from the
Center for Neurologic Diseases at Brigham and Women's Hospital and Harvard Medical School.
Dr. Selkoe, Dr. Shaomin Li, and colleagues examined regulation of a cellular communication
phenomenon known as long-term synaptic depression (LTD). LTD has been linked with neuronal
degeneration, but a role for A? in the regulation of LTD has not been clearly described.
The researchers found that soluble A? facilitated LTD in the hippocampus, a region of the
brain intimately associated with memory. The enhanced synaptic depression induced by
soluble A? was mediated through a decrease in glutamate recycling at hippocampal synapses.
Excess glutamate, the major excitatory neurotransmitter in the brain, is thought to
contribute to the progressive neuronal loss characteristic of AD. The researchers went on
to show that A?-enhanced LTD was mediated by glutamate receptor activity and that the LTD
could be prevented by an extracellular glutamate scavenger system. A very similar
enhancement of LTD could be induced by a pharmacological blocker of glutamate reuptake.
Importantly, soluble A? directly and significantly decreased glutamate uptake by isolated
synapses. "Our findings provide evidence that soluble A? from several sources
enhances synaptic depression through a novel mechanism involving altered glutamate uptake
at hippocampal synapses," concludes Dr. Selkoe. "These results have both
mechanistic and therapeutic implications for the initiation of hippocampal synaptic
failure in AD and in more subtle forms of age-related A? accumulation." Future
studies are needed to determine precisely how soluble A? protein physically interferes
with glutamate transporters at the synapse.
Innovative 3D-imaging technique
captures brain damage linked to Alzheimer's disease
Using an advanced three-dimensional mapping technique developed by UCLA researchers, the
team analyzed magnetic resonance imaging data from 24 patients with amnestic mild
cognitive impairment and 25 others with mild Alzheimer's disease. The research team found
that patients with mild Alzheimer's had 10 to 20 percent more atrophy in most cortical
areas than did MCI patients.
Associate professor of Chemistry Yoshitaka Ishii and his team have isolated an
intermediate structure of the fiber-like amyloid plaques (fibrils) which, they believe,
can be responsible for the nerve cell damage associated with Alzheimer's.
Study Suggests Link Between Smoking
and Alzheimer’s
a new study conducted by Frank M. LaFerla, associate director of the Institute for Brain,
Aging and Dementia at UC Irvine, shows that nicotine may contribute to Alzheimer’s
disease, despite previous research suggesting that nicotine may prevent the crippling
disease.
Alzheimer's disease linked to
mitochondrial damage
Investigators at Burnham Institute for Medical Research (Burnham) have demonstrated that
attacks on the mitochondrial protein Drp1 by the free radical nitric oxide—which
causes a chemical reaction called S-nitrosylation—mediates neurodegeneration
associated with Alzheimer's disease. Prior to this study, the mechanism by which
beta-amyloid protein caused synaptic damage to neurons in Alzheimer's disease was unknown.
These findings suggest that preventing S-nitrosylation of Drp1 may reduce or even prevent
neurodegeneration in Alzheimer's patients. The paper was published in the April 3 issue of
the journal Science. The team of scientists, led by neuroscientist and clinical
neurologist Stuart A. Lipton, M.D., Ph.D., director of the Del E. Webb Center for
Neuroscience, Aging and Stem Cell Research, showed that S-nitrosylated Drp1 (SNO-Drp1)
facilitates mitochondrial fragmentation, damaging regions of nerve cell communication
called synapses. Mitochondria are the energy storehouses of the cell, and their compromise
by excessive fragmentation causes synaptic injury and eventual nerve cell death. Synapses
are critical for learning and memory and their impairment leads to the dementia seen in
Alzheimer's patients. "We now have a better understanding of the mechanism by which
beta-amyloid protein causes neurodegeneration in Alzheimer's disease," said Dr.
Lipton. "We found that beta-amyloid can generate nitric oxide that reacts with Drp1.
By identifying Drp1 as the protein responsible for synaptic injury, we now have a new
target for developing drugs that may slow or stop the progression of Alzheimer's."
Drp1 is an enzyme that mediates fission or fragmentation of mitochondria. The Burnham
researchers showed that excessive production of nitric oxide caused S-nitrosylation of
Drp1 and induced excessive fragmentation of mitochondria in cultured nerve cells or
neurons. The scientists also showed that beta-amyloid protein multimers, which had been
previously implicated in Alzheimer's disease, induced formation of SNO-Drp1. Importantly,
elevated SNO-Drp1 levels were also found in human brains of Alzheimer's patients, but not
in those with Parkinson's disease or controls who didn't have neurodegenerative diseases.
Molecular modeling performed by the team suggested that S-nitrosylation of Drp1 causes
dimerization of the protein and activation of enzymatic activity that induces
mitochondrial fragmentation. To confirm this hypothesis, the scientists showed that RNA
interference to knock down Drp1 or a mutation that prevented Drp1 activity inhibited
excess mitochondrial fragmentation and protected the neurons. Finally, the researchers
showed that a mutated Drp1, lacking the nitrosylation site, did not induce mitochondrial
fragmentation and also prevented neuronal damage. Taken together, these findings suggest
that multimers of beta-amyloid protein induce generation of nitric oxide, which reacts
with Drp1 to cause excessive mitochondrial fragmentation and in turn neuronal damage.
Paradigm Shift in Alzheimers´s
Research opens the Door for New Treatments: Intraneural Aß aggregation triggers neuron
loss
Latest research by Professor Thomas Bayer from University Medicine Center Göttingen
carries the promise of developing new treatments. Alzheimer’s disease (AD) is a
progressive neurodegenerative disorder characterized by extensive neuronal degeneration
and the development of neuritic amyloid plaques and neurofibrillary tangles. Neuronal and
synaptic losses in AD are correlated with dementia and occur in specific brain areas
involved in memory processing. Long-standing evidence shows that progressive cerebral
deposition of Aß plays a seminal role in the pathogenesis of AD. There is great interest,
therefore, in understanding the proteolytic processing of APP, the precursor of Aß, and
its proteases responsible for generating Aß. Ragged peptides with a major species
beginning with phenylalanine at position 4 of Ab have been reported already in 1985 by
Masters et al.1.
Young adults at future risk of
Alzheimer's have different brain activity, says study
Young adults with a genetic variant that raises their risk of developing Alzheimer's
Disease show changes in their brain activity decades before any symptoms might arise,
according to a new brain imaging study by scientists from the University of Oxford and
Imperial College London. The results may support the idea that the brain's memory function
may gradually wear itself out in those who go on to develop Alzheimer's. The research,
published today in the journal Proceedings of the National Academy of Sciences, provides
clues as to why certain people develop Alzheimer's Disease (AD) and it may be a step
towards a diagnostic test that identifies individuals at risk. The degenerative condition
is the most common cause of dementia and it affects around 417,000 people in the UK. The
APOE4 genetic variant is found in about a quarter of the population. Not everyone who
carries the variant will go on to develop AD, but people who inherit one copy of APOE4
have up to four times the normal risk of developing the late-onset variety of the disease.
People who have two copies have around ten times the normal risk. The researchers behind
today's study stress that most carriers of APOE4 will not go on to develop Alzheimer's and
carriers should not be alarmed by the study's findings.
Test quickly assesses whether
Alzheimer's drugs are hitting their target
A test developed by physician-scientists at Washington University School of Medicine in
St. Louis may help assess more quickly the ability of Alzheimer's drugs to affect one of
the possible underlying causes of Alzheimer's disease in humans, accelerating the
development of new treatments. Scientists used the test to show that an Alzheimer's drug
given to healthy volunteers reduced production of a substance known as amyloid beta
(A-beta), a normal byproduct of human metabolism that builds to unhealthy levels forming
brain plaques in Alzheimer's patients. The drug candidate, LY450139, which is also known
as semagacestat, is being studied in clinical trials by Eli Lilly and Company.Ongoing
clinical trials are studying the effect that semagacestat may have on cognitive function
and biochemical and brain imaging biomarkers in patients with Alzheimer's disease.
Washington University researchers wanted to see whether the new measurement technique,
stable isotope-linked kinetics (SILK), could detect the study drug's impact on A-beta
synthesis in healthy volunteers. "Bringing an Alzheimer's disease drug into clinical
trials from tests in animal models has always been challenging," says study director
Randall Bateman, M.D., a Washington University neurologist who treats patients at
Barnes-Jewish Hospital. "We haven't had a way to quickly and accurately assess a
drug's effects, and that meant there always had to be some degree of educated guesswork
when it came to setting the optimal dosage for humans. SILK may help to eliminate much of
that guesswork."
Plaques, Tangles in Brain Don't
Always Lead to Alzheimer's
New British research provides more evidence that the bits of gunk in the brain known as
plaques and tangles don't necessarily lead to Alzheimer's disease, as many experts have
long believed.
Positive Breakthrough for
NuroPro(R) Blood Test for Alzheimer's
This breakthrough, which involved the successful diagnoses of different forms of
Alzheimer's, including high-risk patients, was achieved during the initial phase of
clinical validation trials of the Company's NuroPro(R) AD blood test.
Mount Sinai researchers discover
novel mechanisms that might causally link type 2 diabetes to Alzheimer's disease
A recent study by Mount Sinai faculty suggests that a gene associated with onset of type-2
diabetes also decreases in Alzheimer's disease dementia cases. The research, led by Dr.
Giulio Maria Pasinetti, MD, Ph.D., The Aidekman Family Professor in Neurology, and
Professor of Psychiatry and Geriatrics and Adult Development at Mount Sinai School of
Medicine, was published this week in the scientific journal, Archives of Neurology.
"This new evidence is of extreme interest," Dr. Pasinetti tells us,
"especially because of the evidence that approximately 60% of Alzheimer's disease
dementia cases have at least one serious medical condition primarily associated with
type-2 diabetes, a chronic condition which includes high blood glucose content
(hyperglycemia) and reduced sensitivity to insulin, among other conditions."
"The relationship between type-2 diabetes and Alzheimer's disease is elusive,"
says Dr. Pasinetti. Not all subjects with type-2 diabetes are affected by Alzheimer's
disease, and similarly, not all Alzheimer's disease cases are diabetic. However, in the
last few years, epidemiological evidence indicates that, relative to healthy elderly
subjects, people of the same age affected by type-2 diabetes are twice as likely to
develop Alzheimer's disease dementia. The reason is not known. The new study from Dr.
Pasinetti, reported in this week's issue of Archives of Neurology, provides insight into a
potential mechanism that might explain the relationship between type-2 diabetes and
Alzheimer's disease onset and progression. Dr. Pasinetti and colleagues found that a gene
known as proliferator-activated receptor coactivator 1 - (PGC-1 ), a key regulator of
glucose content currently investigated as a potential therapeutic target for type-2
diabetes, is also decreased in Alzheimer' disease dementia cases. Most importantly, Dr.
Pasinetti reports that PGC-1 decreased in Alzheimer' disease dementia cases with
progression of the clinical disease and positively correlates with brain accumulation of
?-amyloid, an abnormal protein highly linked to Alzheimer' disease dementia and brain
degeneration. This evidence is of high interest to the field and suggests, for the first
time, a strong relationship between decreased content of a gene responsible for type-2
diabetes in Alzheimer's disease dementia cases, says Dr. Pasinetti.
Non-drug treatment of
Alzheimer’s disease - long-term benefit not proven
Reliable conclusions about the potential for benefit and harm are currently not possible /
In general there is still a great need for good studies on non-drug interventions. Whether
people with Alzheimer's disease benefit in the long term from non-drug treatment
interventions remains an unanswered question. This unsatisfactory finding is mainly due to
the fact that convincing studies are lacking so far. For individual approaches, the
studies provide indications of a benefit, but also of harm. This is the result of the
final report by the Institute for Quality and Efficiency in Health Care (IQWiG) published
on 17 March 2009. According to IQWiG, a general problem of the benefit assessment of
non-drug treatment interventions is particularly shown in the therapy of Alzheimer's
disease: small research budgets and an underdeveloped study methodology lead to the
situation that even for procedures with potential, no reliable conclusions can be drawn
and thus no proof of a benefit can be provided.
Umbilical cord blood cell therapy
may reduce signs and symptoms of Alzheimer's disease
Targeted immune suppression using human umbilical cord blood cells significantly improved
Alzheimer's-like brain damage in a mouse model of the neurodegenerative disease, a new
study reports.
New findings resolve long dispute
about how the disease might kill brain cells
For a decade, Alzheimer's disease researchers have been entrenched in debate about one of
the mechanisms believed to be responsible for brain cell death and memory loss in the
illness. Now researchers at the University of Michigan and the University of California,
San Diego have settled the dispute. Resolving this controversy improves understanding of
the disease and could one day lead to better treatments. Michael Mayer, an assistant
professor in the U-M departments of Biomedical Engineering and Chemical Engineering, and
Jerry Yang, an assistant professor in the Department of Chemistry and Biochemistry at
UCSD, and their colleagues found a flaw in earlier studies supporting one side of the
debate. Their findings are published online in the Journal of Neurotoxicity Research. They
will appear in the May print edition. Their results clarify how small proteins called
amyloid-beta peptides damage brain cell membranes, allowing extra calcium ions to enter
the neurons. An ion is an electrically-charged particle. An ion imbalance in a cell can
trigger its suicide. Amyloid-beta peptides are the prime suspects for causing cell death
in Alzheimer's, although other mechanisms could also be to blame. The disease is not well
understood. The researchers confirmed evidence found by others that amyloid-beta peptides
prick pores into brain cell membranes, opening channels where calcium ions can rush in.
This was one mechanism the field had contemplated, but other evidence suggested a
different scenario. Some researchers believed that the peptide caused a general thinning
of the cell membranes and these thinned membranes lost their ability to keep calcium ions
out of brain cells. Mayer and Yang disproved this latter theory. "When you understand
these mechanisms better, you have a better chance of being able to pharmaceutically
counteract them as a possible treatment. For instance, if amyloid-beta thins membranes,
this general effect might be difficult to treat. On the other hand, if it forms pores,
this effect might be treatable with pore blockers. Ion channel blockers are medications
sold today to treat a variety of diseases," Mayer said. He cautions that much
research is needed before it is known whether such medications are effective and safe to
treat Alzheimer's. Mayer and Yang were able to explain the other experimental results that
blamed cell membrane thinning for uncontrolled calcium ion fluctuations. It turns out that
in these studies, trace amounts of residual solvent used to prepare the peptide had a
dramatic effect. The Michigan- and UCSD-led team reproduced these experimental results
using only the solvent, without the peptide. The solvent is called Hexafluoroisopropanol,
or HFIP."HFIP is a good solvent used to break up clumps of the peptide to prepare for
experiments, but it's toxic and membrane-active. What we found was that the reported
preparation procedure did not remove the solvent effectively," Mayer said. "Our
findings are watertight since we could reproduce the thinning effect in the absence of
amyloid-beta peptides by this solvent alone."
Study validates Pittsburgh
Compound-B in identifying Alzheimer's disease brain toxins
A groundbreaking study conducted by University of Pittsburgh Alzheimer's disease
researchers reported in the journal Brain (currently online) confirms that Pittsburgh
Compound-B binds to the telltale beta-amyloid deposits found in the brains of patients
with Alzheimer's disease. The finding is a significant step toward enabling clinicians to
provide a definitive diagnosis of Alzheimer's disease in living patients.
Low level of neuronal receptor
linked to mild cognitive impairment and Alzheimer's disease
Results of a new study indicate a strong link between the loss of the neuronal receptor
LR11and onset of mild cognitive impairment (MCI), often a harbinger of Alzheimer's
disease. The findings also show that levels of LR11 in the brain tissue reflect the
severity of cognitive impairment and may predict which individuals will progress to
Alzheimer's disease.
Study Confirms Validity of
Pittsburgh Compound-B in Identifying the Toxins Associated with Alzheimer’s Disease
A groundbreaking study conducted by University of Pittsburgh Alzheimer’s disease
researchers reported in the journal Brain (currently online) confirms that Pittsburgh
Compound-B (PiB) binds to the telltale beta-amyloid deposits found in the brains of
patients with Alzheimer’s disease. The finding is a significant step toward enabling
clinicians to provide a definitive diagnosis of Alzheimer’s disease in living
patients.
People who smoke are more likely to develop Alzheimer's disease or dementia than
nonsmokers or those who smoked in the past, according to a study published in the Sept. 4,
2007, issue of Neurology, the medical journal of the American Academy of Neurology.
Mice with Alzheimer's disease
suffer 'silent' seizures
Mice genetically engineered to have a disease like Alzheimer's have "silent"
seizures that appear related to cellular changes involving the excess accumulations of the
protein amyloid beta, said researchers from the Gladstone Institute of Neurological
Disease and Baylor College of Medicine in a report that appears in today's issue of the
journal Neuron.
Insulin is a Possible New Treatment
for Alzheimer’s
A Northwestern University-led research team reports that insulin, by shielding
memory-forming synapses from harm, may slow or prevent the damage and memory loss caused
by toxic proteins in Alzheimer’s disease. The findings, which provide additional new
evidence that Alzheimer’s could be due to a novel third form of diabetes, will be
published online the week of Feb. 2 by the Proceedings of the National Academy of Sciences
(PNAS). In a study of neurons taken from the hippocampus, one of the brain’s crucial
memory centers, the scientists treated cells with insulin and the insulin-sensitizing drug
rosiglitazone, which has been used to treat type 2 diabetes. (Isolated hippocampal cells
are used by scientists to study memory chemistry; the cells are susceptible to damage
caused by ADDLs, toxic proteins that build up in persons with Alzheimer’s disease.)
The researchers discovered that damage to neurons exposed to ADDLs was blocked by insulin,
which kept ADDLs from attaching to the cells. They also found that protection by low
levels of insulin was enhanced by rosiglitazone. ADDLs (short for “amyloid
beta-derived diffusible ligands”) were discovered at Northwestern and are known to
attack memory-forming synapses. After ADDL binding, synapses lose their capacity to
respond to incoming information, resulting in memory loss.
Research on link between vitamin D
and Alzheimer’s ‘warranted’
A California scientist has been arguing there is a good reason to conduct more in-depth
research on the possible causative link between vitamin D levels and the development of
Alzheimer’s disease.
Humanin peptide linked to neuronal
cell survival and regulation of glucose metabolism
Recent studies have shown that the mitochondrial peptide Humanin (HN) protects against
neuronal cell death such as happens in Alzheimer's disease. Now, in a study presented
April 22 at Experimental Biology 2009 in New Orleans, Dr. Nir Barzilai reports that a
small infusion of HN is the most potent regulator of insulin metabolism that his research
team has ever seen, significantly improving overall insulin sensitivity and sharply
decreasing the glucose levels of diabetic rats. The finding is the first evidence of a
role for HN in glucose metabolism and provides new insight into how this metabolism may be
involved in the development of seemingly diverse age-related diseases such as Type 2
Diabetes Mellitus and Alzheimer's. The finding also provides support for the growing
understanding that the brain (not just the pancreas, liver and other peripheral organs) is
heavily involved in glucose metabolism. Furthermore, says Dr. Barzilai, the Ingeborg and
Ira Leon Rennert Chair of Aging Research and Director of the Institute for Aging Research
at the Albert Einstein College of Medicine, the power of HN on insulin action suggests a
new therapeutic approach to diabetes. Further understanding of how HN interactions with
the growth hormone/insulin-like growth factor system may also lead to strategies to
protect against age-related diseases including Alzheimer's.
Blocking formation of toxic plaques
implicated in type 2 diabetes
Amid growing evidence that the same abnormal clumping of proteins in Alzheimer’s
disease also contributes to type-2 diabetes, scientists in New York are reporting
discovery of a potent new compound that reduces formation of those so-called amyloid
plaques. Their study is scheduled for the Sept. 5 issue of the Journal of the American
Chemical Society, a weekly publication.The report cites evidence correlating increases in
amyloid formation in the pancreas with increases in severity and rate of progression of
type-2 diabetes, which affects almost 20 million Americans and is rapidly rising
worldwide. Deposits of the abnormal protein damage and destroy insulin-producing
“islet” cells in the pancreas. Researchers have been seeking potential new
medicines that block formation of an abnormal, misfolded protein called islet amyloid
polypeptide (IAPP), which may play a key role in the cell destruction.
Mediterranean diet may help
Alzheimer's patients live longer
A Mediterranean diet may help people with Alzheimer’s disease live longer than
patients who eat a more traditional Western diet. The study is published in the September
11, 2007, issue of Neurology, the medical journal of the American Academy of Neurology.
Mayo Clinic Researchers Find Agents
that Speed Up Destruction of Proteins Linked to Alzheimer's Disease
Taking a new approach to the treatment and prevention of Alzheimer's disease, a research
team led by investigators at the Mayo Clinic campus in Florida has shown that druglike
compounds can speed up destruction of the amyloid beta (A-beta) proteins that form plaque
in the brains of patients with the disorder. Researchers say their study, published in the
April 22 online issue of PLoS ONE, demonstrates that this strategy is a viable and
exciting alternative to the approach most drug designers have taken to date.
Increased Level Of Magnetic Iron
Oxides Found In Alzheimer’s Disease
A team of scientists, led by Professor Jon Dobson, of Keele University in Staffordshire,
UK, have found, for the first time, raised levels of magnetic iron oxides in the part of
the brain affected by Alzheimer's Disease (AD). Their research has also shown that this
association was particularly strong in females compared to males. The group speculates
that this may be a result of gender differences in the way the body handles and stores
iron. Though the results are based on a small number of samples, they give an indication
that iron accumulation associated with Alzheimer's appears to involve the formation of
strongly magnetic iron compounds. As these compounds have a strong effect on MRI signal
intensity, with further study, it may be possible to use this as a biomarker for the
development of an MRI-based Alzheimer's diagnostic technique.
Study explores computers to detect
Alzheimer's in brain scans
Computers can be trained to detect early signs of Alzheimer's disease in MRI brain scans,
according to a study from Mayo Clinic and other participating centers. The findings were
published in the March 2008 issue of Brain.
UCSB scientists make headway in
understanding Alzheimer's disease
Scientists at UC Santa Barbara have discovered that a protein called BAG2 is important for
understanding Alzheimer's disease and may open up new targets for drug discovery. They are
ready to move from studying these proteins in culture to finding out how they work with
mice. In a paper published this week in the Journal of Neuroscience, the scientists
describe important activities of BAG2 in cleaning up brain cells. The protein tau is
normally found in brain cells, but scientists don't know why it clumps into tangles in
people with Alzheimer's disease. Senior author Kenneth S. Kosik, co-director of UCSB's
Neuroscience Research Institute, and Harriman Chair in Neuroscience, has been involved in
the study of neurons that develop neurofibrillary tangles, one of the hallmarks of the
disease, since he was a postdoctoral fellow. "Early on in my career, we were one of
several labs to discover that tau was in the neurofibrillary tangles," said Kosik.
Kosik's team recently started to work on BAG2 to find out how it may be involved in the
removal of tangled tau. "It turns out that when you put this protein into the cell,
it clears away the damaged tau very nicely," said Kosik. It doesn't clear away all
the tau; it goes for the damaged tau protein and removes it.
Researchers find possible
environmental causes for Alzheimer's, diabetes
A new study by researchers at Rhode Island Hospital have found a substantial link between
increased levels of nitrates in our environment and food with increased deaths from
diseases, including Alzheimer's, diabetes mellitus and Parkinson's. The study was
published in the Journal of Alzheimer's Disease (Volume 17 - July 2009). Led by Suzanne de
la Monte, MD, MPH, of Rhode Island Hospital, researchers studied the trends in mortality
rates due to diseases that are associated with aging, such as diabetes, Alzheimer's,
Parkinson's, diabetes and cerebrovascular disease, as well as HIV. They found strong
parallels between age adjusted increases in death rate from Alzheimer's, Parkinson's, and
diabetes and the progressive increases in human exposure to nitrates, nitrites and
nitrosamines through processed and preserved foods as well as fertilizers. Other diseases
including HIV-AIDS, cerebrovascular disease, and leukemia did not exhibit those trends. De
la Monte and the authors propose that the increase in exposure plays a critical role in
the cause, development and effects of the pandemic of these insulin-resistant diseases. De
la Monte, who is also a professor of pathology and lab medicine at The Warren Alpert
Medical School of Brown University, says, "We have become a 'nitrosamine generation.'
In essence, we have moved to a diet that is rich in amines and nitrates, which lead to
increased nitrosamine production. We receive increased exposure through the abundant use
of nitrate-containing fertilizers for agriculture." She continues, "Not only do
we consume them in processed foods, but they get into our food supply by leeching from the
soil and contaminating water supplies used for crop irrigation, food processing and
drinking." Nitrites and nitrates belong to a class of chemical compounds that have
been found to be harmful to humans and animals. More than 90 percent of these compounds
that have been tested have been determined to be carcinogenic in various organs. They are
found in many food products, including fried bacon, cured meats and cheese products as
well as beer and water. Exposure also occurs through manufacturing and processing of
rubber and latex products, as well as fertilizers, pesticides and cosmetics. Nitrosamines
are formed by a chemical reaction between nitrites or other proteins. Sodium nitrite is
deliberately added to meat and fish to prevent toxin production; it is also used to
preserve, color and flavor meats. Ground beef, cured meats and bacon in particular contain
abundant amounts of amines due to their high protein content. Because of the significant
levels of added nitrates and nitrites, nitrosamines are nearly always detectable in these
foods. Nitrosamines are also easily generated under strong acid conditions, such as in the
stomach, or at high temperatures associated with frying or flame broiling. Reducing sodium
nitrite content reduces nitrosamine formation in foods. Nitrosamines basically become
highly reactive at the cellular level, which then alters gene expression and causes DNA
damage. The researchers note that the role of nitrosamines has been well-studied, and
their role as a carcinogen has been fully documented. The investigators propose that the
cellular alterations that occur as a result of nitrosamine exposure are fundamentally
similar to those that occur with aging, as well as Alzheimer's, Parkinson's and Type 2
diabetes mellitus.
Caffeine reverses memory impairment
in Alzheimer's mice
Coffee drinkers may have another reason to pour that extra cup. When aged mice bred to
develop symptoms of Alzheimer's disease were given caffeine – the equivalent of five
cups of coffee a day – their memory impairment was reversed, report University of
South Florida researchers at the Florida Alzheimer's Disease Research Center. Back-to-back
studies published online today in the Journal of Alzheimer's Disease, show caffeine
significantly decreased abnormal levels of the protein linked to Alzheimer's disease, both
in the brains and in the blood of mice exhibiting symptoms of the disease. Both studies
build upon previous research by the Florida ADRC group showing that caffeine in early
adulthood prevented the onset of memory problems in mice bred to develop Alzheimer's
symptoms in old age. "The new findings provide evidence that caffeine could be a
viable 'treatment' for established Alzheimer's disease, and not simply a protective
strategy," said lead author Gary Arendash, PhD, a USF neuroscientist with the Florida
ADRC. "That's important because caffeine is a safe drug for most people, it easily
enters the brain, and it appears to directly affect the disease process." Based on
these promising findings in mice, researchers at the Florida ADRC and Byrd Alzheimer's
Center at USF hope to begin human trials to evaluate whether caffeine can benefit people
with mild cognitive impairment or early Alzheimer's disease, said Huntington Potter, PhD,
director of the Florida ADRC and an investigator for the caffeine studies. The research
group has already determined that caffeine administered to elderly non-demented humans
quickly affects their blood levels of ?-amyloid, just as it did in the Alzheimer's mice.
"These are some of the most promising Alzheimer's mouse experiments ever done showing
that caffeine rapidly reduces beta amyloid protein in the blood, an effect that is
mirrored in the brain, and this reduction is linked to cognitive benefit," Potter
said. "Our goal is to obtain the funding needed to translate the therapeutic
discoveries in mice into well-designed clinical trials."
New way to diagnose Alzheimer's
disease promises earlier treatment
Physicians may be able to detect and treat Alzheimer's in its earliest stages, when
patients are experiencing only mild degrees of cognitive impairment, thanks to new
diagnostic criteria proposed by an international group of researchers.
Novel role of protein in generating
amyloid-beta peptide
A defining hallmark of Alzheimer's disease is the accumulation of the amyloid ? protein
(A?), otherwise known as "senile plaques," in the brain's cortex and
hippocampus, where memory consolidation occurs. Researchers at the University of
California, San Diego School of Medicine have identified a novel protein which, when
over-expressed, leads to a dramatic increase in the generation of A?. Their findings,
which indicate a potential new target to block the accumulation of amyloid plaque in the
brain, will be published in the May 1 issue of the Journal of Biological Chemistry.
"The role of the multi-domain protein, RANBP9, suggests a possible new therapeutic
target for Alzheimer's disease," said David E. Kang, PhD, assistant professor of
neurosciences at UC San Diego and director of this study. The neurotoxic protein A? is
derived when the amyloid precursor protein (APP) is "cut" by two enzymes,
?-secretase (or BACE) and ?-secretase (or Presenilin complex.) However, inhibiting these
enzymes in order to stop the amyloid cascade has many negative side effects, as these
enzymes also have various beneficial uses in brain cells. So the researchers looked for an
alternative way to block the production of amyloid beta. In order for cleavage to occur,
the APP needs to travel to cholesterol-enriched sites within the cell membrane called
RAFTS, where APP interacts with the two enzymes. It is this contact that the researchers
sought to block. Kang explains that the researchers identified the RANBP9 protein by
studying low density lipoprotein receptor-related protein (LRP), a protein that rapidly
shuttles A? out of the brain and across the blood-brain barrier to the body, where it
breaks down into harmless waste products. A small segment of LRP can also stimulate A?
generation, and the scientists narrowed this segment down to a 37-amino-acid stretch that
can lead to changes in A?. "RANBP9 is one of the proteins we identified that
interacted with this LRP segment, but one that had never before been associated with
disease-related neuronal changes," said Kang. "We discovered that this protein
interacts with three components involved in A? generation – LRP, APP and BACE1 –
and appears to 'scaffold' them into a structure." Kang explained that these three
components must come together to result in the first cut or cleaving that leads to
production of A?. To test this, the scientists knocked out RANBP9 in the cell, and
discovered that 60% less A? was produced. "This unique factor enhances the production
of beta amyloid," said Kang. "Inhibiting the RANBP9 protein may offer an
alternative approach to therapy, by preventing contact between APP and the enzyme that
makes the cut essential to produce amyloid plaques." The researchers' next step is to
verify these findings in animal models.
Growth factor protects key brain
cells in Alzheimer's models
Memory loss, cognitive impairment, brain cell degeneration and cell death were prevented
or reversed in several animal models after treatment with a naturally occurring protein
called brain-derived neurotrophic factor (BDNF). The study by a University of California,
San Diego-led team – published in the February 8, 2009 issue of Nature Medicine
– shows that BDNF treatment can potentially provide long-lasting protection by
slowing, or even stopping the progression of Alzheimer's disease in animal models.
"The effects of BDNF were potent," said Mark Tuszynski, MD, PhD, professor of
neurosciences at the UC San Diego School of Medicine and neurologist at the Veterans
Affairs San Diego Health System. "When we administered BDNF to memory circuits in the
brain, we directly stimulated their activity and prevented cell death from the underlying
disease." BDNF is normally produced throughout life in the entorhinal cortex, a
portion of the brain that supports memory. Its production decreases in the presence of
Alzheimer's disease. For these experiments, the researchers injected the BDNF gene or
protein in a series of cell culture and animal models, including transgenic mouse models
of Alzheimer's disease; aged rats; rats with induced damage to the entorhinal cortex; aged
rhesus monkeys, and monkeys with entorhinal cortex damage. In each case, when compared
with control groups not treated with BDNF, the treated animals demonstrated significant
improvement in the performance of a variety of learning and memory tests. Notably, the
brains of the treated animals also exhibited restored BDNF gene expression, enhanced cell
size, improved cell signaling, and activation of function in neurons that would otherwise
have degenerated, compared to untreated animals. These benefits extended to the
degenerating hippocampus where short-term memory is processed, one of the first regions of
the brain to suffer damage in Alzheimer's disease.
MRI shows brain atrophy pattern
that predicts Alzheimer's
Using special MRI methods, researchers have identified a pattern of regional brain atrophy
in patients with mild cognitive impairment (MCI) that indicates a greater likelihood of
progression to Alzheimer's disease. The findings are published in the online edition of
Radiology. "Previously, this pattern has been observed only after a diagnosis of
probable Alzheimer's disease," said the study's lead author, Linda K. McEvoy, Ph.D.,
assistant project scientist in the Department of Radiology at the University of California
San Diego School of Medicine in La Jolla. "Our results show that some individuals
with MCI have the atrophy pattern characteristic of mild Alzheimer's disease, and these
people are at higher risk of experiencing a faster rate of brain degeneration and a faster
decline to dementia than individuals with MCI who do not show that atrophy
pattern."According to the Alzheimer's Association, more than five million Americans
currently have Alzheimer's disease. One of the goals of modern neuroimaging is to help in
early and accurate diagnosis, which can be challenging. There is no cure for Alzheimer's
disease, but when it is diagnosed early, drug treatment may help improve or stabilize
patient symptoms. In Alzheimer's disease, nerve cell death and tissue loss cause areas of
the brain to atrophy. Structural MRI allows radiologists to visualize subtle anatomic
changes in the brain that signal atrophy. MCI is associated with an increased risk of
progression to Alzheimer's disease. Rates of progression vary. Some patients progress
rapidly, while others remain stable for relatively long periods of time.
Researchers at UC Santa Barbara and other institutions have found evidence that a certain
cluster of peptides--short chains of amino acids linked together--may be a toxic agent
producing Alzheimer’s disease.
A new study by the Buck Institute for Age Research in Novato provides insight into the
cause of Alzheimer's disease and suggests it may be possible to short-circuit the
molecular mechanism that underlies it.
New method to stimulate immune
system may be effective at reducing amyloid burden in Alzheimer’s
Researchers at NYU Langone Medical Center have discovered a novel way to stimulate the
innate immune system of mice with Alzheimer's disease (AD) - leading to reduced amyloid
deposits and the prevention of Alzheimer's disease related pathology - without causing
toxic side effects. The study entitled "Induction of Toll-like Receptor 9 Signaling
as a Method for Ameliorating Alzheimer's Disease Related Pathology" was published in
The Journal of Neuroscience. NYU Langone researchers stimulated the innate immune system
via the Toll-like 9 receptor (TLR9) via treatment with cytosine-guanosine containing DNA
oligodeoxynucleotides (CpG ODNs) in Tg2576 AD model transgenic mice. This treatment
produced a 66% and 80% reduction in the cortical and vascular amyloid burden, when
compared with non-treated AD mice. Also, vaccinated Tg2576 mice performed similarly to
non-treated mice on a radial arm maze used in the study, showing improvements in behavior
and reduced amyloid burden. "Our results indicate that stimulation of the innate
immune system through TLR9 with CpG ODNs is an effective and apparently non-toxic method
to reduce the amyloid burden in the brain," said Thomas Wisniewski, MD, professor of
neurology, pathology and psychiatry at NYU Langone Medical Center. "Furthermore we
found that amyloid reduction was associated with significant cognitive benefits in an AD
mouse model. This approach has significant implications for future human immunomodulatory
approaches to prevent AD in humans." The deposition of amyloid ? (A?) in the central
nervous system in the form of amyloid plaques is a hallmark of Alzheimer's disease. A?
accumulation destroys neurons in the brain, leading to deficits in cognitive abilities.
Immunomodulation or vaccination for AD is emerging as an effective means of shifting the
equilibrium from A? accumulation to clearance; however, excessive cell mediated
inflammation and cerebral microhemorrhages - two forms of toxicity- were shown to occur in
previous vaccination studies targeting the adaptive immune system.
New study provides insight into
ways organ systems outside the brain may affect Alzheimer's disease
In Alzheimer's disease the brain accumulates a molecule called A-beta that can be quite
toxic to brain cells. Many researchers believe that finding ways to clear A-beta may be a
key to treatment or prevention of Alzheimer's disease. A study published in the February
issue of the Journal of Alzheimer's Disease provides new insights into the way A-beta in
the peripheral blood stream affects A-beta clearance in the brain. Scientists from the
University of Washington in Seattle, VA Puget Sound Health Care System, and the University
of Hong Kong found that when circulating A-beta levels in the blood stream of rats were
elevated, known amounts of radioactively tagged A-beta were swept from the brain more
slowly. These findings directly demonstrate something researchers have proposed for
several years now—that freely circulating A-beta concentrations outside the brain can
regulate A-beta clearance rates inside the central nervous system. Researchers are coming
to appreciate that the brain does not act alone in the task of clearing A-beta . It can be
shuttled back and forth between compartments inside the brain and the peripheral blood
supply where A-beta interacts with other organ systems. Treatments that increase the flow
of A-beta away from the brain hold great therapeutic promise. Despite the promise of such
work many basic questions still need to be answered about how the brain interacts with the
rest of body to hold A-beta in check.
Gladstone scientists find potential
strategy to eliminate poisonous protein from Alzheimer brains
Scientists at the Gladstone Institute of Neurological Disease (GIND) have identified a new
strategy to destroy amyloid-beta (AB) proteins, which are widely believed to cause
Alzheimer's disease (AD). Li Gan, PhD, and her coworkers discovered that the activity of a
potent AB-degrading enzyme can be unleashed in mouse models of the disease by reducing its
natural inhibitor cystatin C (CysC). All of us produce AB proteins in the brain. However,
in most people, the proteins never build up to dangerous levels because they are cleared
away by enzymes that destroy them. Previously Dr. Gan's laboratory had shown that
cathepsin B (CatB) is such an AB-degrading enzyme. In the latest issue of the journal
Neuron, the researchers report a highly effective approach to promote CatB-mediated
clearance of AB . "Many groups have developed drugs to block the production of AB,
but the efficacy and safety of this approach remains to be demonstrated in clinical
trials," said GIND Director Lennart Mucke, MD "By identifying an effective
strategy to enhance the removal of AB, this research provides a very promising alternative
or complementary therapeutic avenue." High levels of AB in the brain may result from
overproduction of AB or from an inability to eliminate it from the brain. While most work
has focused on the first option, the latter has been problematic. For example, efforts to
develop a vaccine that would trigger the immune system to eliminate AB have shown limited
success and resulted in adverse side effects. "Our strategy to harness the activity
of a powerful AB-degrading enzyme takes advantage of the brain's own defense system to
remove the toxic AB build-up," said Dr. Gan. "In principle, one could boost the
activity of CatB by expressing more of it in the brain or by reducing the activity of
CysC, its natural inhibitor. We focused on the latter strategy because it has greater
long-term therapeutic potential." Many enzymes that degrade proteins are kept in
check by regulators called protease inhibitors. The activity of CatB is regulated by the
protease inhibitor CysC. By reducing CysC activity, the scientists were able to unleash
the AB-degrading power of CatB, effectively preventing the build-up of AB in mouse models
of AD.
Inflammation may trigger
Alzheimer's disease, Saint Louis University findings suggest
The anti-inflammatory drug indomethacin could hold promise as a treatment for Alzheimer's
disease, says a Saint Louis University doctor and researcher. Two research studies
published by William A. Banks, M.D., professor of geriatrics and pharmacological and
physiological science at Saint Louis University School of Medicine, support this
conclusion and offer what he calls a "one-two punch" in giving clues on how
Alzheimer's disease develops and could be treated. His study in the July edition of the
Journal of Alzheimer's Disease supports the idea that toxic levels of amyloid beta
protein, the substance scientists believe is responsible for Alzheimer's disease,
accumulate in the brain because a pump that pushes it into the blood and past the
blood-brain barrier malfunctions. The blood-brain barrier is a system of cells that
regulates the exchange of substances between the brain and the blood. The blood-brain
barrier transporter known as LRP is the pump that removes amyloid beta protein from the
brain and into the bloodstream. "LRP malfunctions like a stop light stuck on red, and
keeps amyloid beta protein trapped in the brain," said Banks, who also is a staff
physician at Veterans Affairs Medical Center in St. Louis. He tested the hypothesis by
giving mice an antisense, which is a molecular compound that blocked the production of
LRP. Amyloid beta protein accumulated in the brain and the mice showed memory loss and
learning impairment. The finding raises the question of what causes LRP to malfunction.
Banks' study in the May issue of Brain Behavior and Immunity suggests inflammation as the
culprit and supports using indomethacin, an anti-inflammatory medication, as a buffer to
protect LRP from being turned off. Inflammation, which is part of the body's natural
immune response, occurs when the body activates white blood cells and produces chemicals
to fight infection and invading foreign substances.
Forgotten and lost - when proteins
"shut down" our brain
Which modules of the tau protein, in neurons of Alzheimer disease patients, may act in a
destructive manner were investigated by researchers from the Max Planck Institute for
Biophysical Chemistry (Göttingen) and the Max Planck Unit for Structural Molecular
Biology (Hamburg) with the help of Nuclear Magnetic Resonance Spectroscopy (PLoS Biology,
February 17, 2009). Coordination becomes difficult, items disappear, keeping new
information in the mind is impossible. Worldwide almost 30 million people suffer from
Alzheimer’s disease, a neurodegenerative, irreversible ailment which starts with
memory gaps and ends in helplessness and the loss of personality. The most critical factor
in developing Alzheimer’s disease is age. Most cases occur after the age of 65. Two
hallmarks are typical for Alzheimer affected brains. One of them, located between nerve
cells, is amyloid plaques - extracellular protein aggregates mainly composed of a protein
named beta-amyloid. The other clue is intracellular tau fibrils. In the interplay with
genetic factors, the latter contribute to a disordered communication within the cell. This
triggers cell death. But the tau protein is not only harmful. Quite the contrary is the
case. In its normal non-pathogenic form tau binds to microtubules, long tubular
cytoskeletal building blocks, which serve as "tracks" for intracellular
transport. In patients afflicted by Alzheimer’s disease or similar dementia, tau is
abnormally altered. In its pathogenic form tau possesses more phosphorylated amino acids
than in its normal healthy counterpart. "Our interest was focussed on how certain
phosphorylated residues alter the structure of tau in a way that it can not bind to
microtubules anymore" explains Markus Zweckstetter at the Max Planck Institute for
Biophysical Chemistry.
Most neuropsychological tests don't
tell Alzheimer's disease from vascular dementia
Most of the cognitive tests that have been used to decide whether someone has Alzheimer's
disease or vascular dementia have not been very helpful when used alone. A new report
published by the American Psychological Association concluded that when older people are
confused and forgetful, doctors should base their diagnoses on many different types of
information, including medical history and brain imaging. Both Alzheimer's disease and
vascular dementia affect learning and memory, behavior and day-to-day function. Even so,
they're caused by different problems in the brain and require different medical
approaches. It's important to tell them apart accurately, stresses the study in July's
Neuropsychology. Valid diagnoses can help doctors treat patients more effectively, and
help patients and families better understand their situations. Jane Mathias, PhD, and
Jennifer Burke, M.Psych.(Clinical), both from the University of Adelaide, analyzed 81
previously published studies that compared the cognitive testing of people diagnosed with
dementia of the Alzheimer's (4,867) and vascular type (2,263). The average age across
participants was 75. Of the 118 different tests that were used in more than one study,
Mathias and Burke found that only two were able to adequately differentiate between
Alzheimer's and vascular dementia. The Emotional Recognition Task (the ability to identify
facial expressions in photographs and match emotional expressions to situations, at which
people with Alzheimer's were better) and Delayed Story Recall (at which people with
vascular dementia were better), were the only tests that appeared to reliably tell the two
groups apart.
Ground-breaking Alzheimer's
findings reveal new treatment strategy
Alzheimer’s disease affects the major two types of brain cells, neurones and
neuroglia. For a long time glial cells have been thought to have a purely supportive role.
However, recent work and more specifically ongoing studies at the University of Manchester
are probing a much more relevant functional role including new treatment opportunities,
for neurodegenerative processes such as Alzheimer’s disease. Dr José J. Rodríguez
Arellano and Professor Alexei Verkhratsky believe that, contrary to popular belief,
neuroglial cells (astrocytes) in the brain shrink during Alzheimer’s disease.
Astrocytes are vital in providing for generation and maintenance of synapses and therefore
diminished astroglial support alters synaptic connectivity thus redusing brain cognitive
power. They say that probably the new strategies aimed at protection and support of
neuroglia may help to combat brain degeneration in Alzheimer disease. Dr
Rodriguez-Arellano, whose work was funded by the Alzheimer’s Research Trust, says:
“These are amazing findings and totally unexpected. We have found that model animals
(transgenic mice) with Alzheimer’s pathology have problems with glial cells as well
as with the neurones in the brain. “Everybody thought that glial cells grew bigger in
response to the disease but we have found that some of them actually shrink and this
causes serious problems. Glial cells are not merely supportive; they have an active role
in maintaining synapses so the imbalance of these cells can have a serious negative
effect.”
Researchers surprised by similar
structures in Sanfilippo syndrome and Alzheimer's disease
Researchers seeking to understand the causes of a rare genetic lysosomal storage disease,
Sanfilippo syndrome type B, were surprised to find protein aggregates, known as
neurofibrillary tangles, that are usually seen in Alzheimer's and other forms of dementia,
according to a study published May 4 in the Proceedings of the National Academy of
Sciences. The discovery, in a study conducted at the Los Angeles Biomedical Research
Institute (LA BioMed) and the University of California, Los Angeles (UCLA), means that the
childhood dementia often seen in lysosomal storage diseases may have mechanisms similar to
those found in Alzheimer's disease and other age-related dementias, which are
characterized by an abnormal accumulation of the protein, P-tau. The scientists also said
these findings mean those suffering from these rare disorders could one day benefit from
the abundance of research underway for the growing numbers of Alzheimer's patients.
Increased level of magnetic iron
oxides found in Alzheimer's disease
A team of scientists, led by Professor Jon Dobson, of Keele University in Staffordshire,
UK, have found, for the first time, raised levels of magnetic iron oxides in the part of
the brain affected by Alzheimer's Disease. The results of their research have been
published in the Journal of Alzheimer's Disease
GPS Shoes - Tracking Parents With
Alzheimer's Disease
a designer of orthopedic footwear and a GPS tracking manufacturer have just announced an
agreement to develop GPS-embedded orthopedic footwear for seniors with dementia. Aetrex®
and GTX™ corporations formed their partnership to enable loved ones and caretakers to
know where the Alzheimer's patient is at all times, with almost-certainty that his or her
shoes will not be removed.
How neuronal activity leads to
Alzheimer's protein cleavage
Amyloid precursor protein, whose cleavage product, amyloid-b, builds up into fibrous
plaques in the brains of Alzheimer's disease patients, jumps from one specialized membrane
microdomain to another to be cleaved, report Sakurai et al in the Journal of Cell Biology.
Discovery of brain protein may be
clue to treatment
A study from the Buck Institute for Age Research offers a revolutionary new model for
Alzheimer’s disease (AD), a devastating neurodegenerative disorder which afflicts 24
million people worldwide. In an effort to unravel the normal function of a protein
implicated in AD, scientists in California and France have discovered a naturally
occurring protein that provides a new therapeutic target for the disease. The finding
upsets the current theory that AD is a disease of toxicity stemming from damage caused by
sticky plaques that collect in the brain – this research points to the condition as a
disorder involving an imbalance in signaling between neurons. The study appears online in
the Nature publication Cell Death and Differentiation. One of the mysteries of AD has been
the normal function of the amyloid precursor protein (APP) which are concentrated at the
points where neurons connect. Even though the sticky amyloid plaques which have been
viewed as a hallmark sign of AD result from APP, it seems unlikely that APP exists simply
to cause Alzheimer’s disease. In their study, scientists from the Buck Institute and
the CNRS (Centre Nationale de la Recherche Scientifique) show that APP binds to netrin-1,
a protein that helps to guide nerves and their connections in the brain, as well as
helping nerve cells to survive. When netrin-1 was given to mice that have a gene for
Alzheimer’s disease their symptoms were reversed, and the sticky amyloid was reduced.
These results suggest that the long-held belief that AD is caused by brain cell damage
inflicted by the amyloid plaques may be wrong; instead, it is beginning to appear that the
disease stems from an imbalance between the normal making and breaking of connections in
the brain, with netrin-1 supporting the connections and the amyloid breaking the
connections -- both by binding to APP and activating normal cell programs. Not only did
the netrin-1 binding to APP keep the nerve cells alive and connected, but it also shut
down the production of the amyloid, all of which makes it an interesting potential
therapeutic.
Radiologists identify early brain
marker of Alzheimer's disease
Researchers using functional magnetic resonance imaging have found a new marker which may
aid in early diagnosis of Alzheimer's disease, according to a study published in the
October issue of Radiology.
Gladstone scientists identify role
of fatty acids in Alzheimer's disease
Scientists at the Gladstone Institute of Neurological Disease and the University of
California have found that complete or partial removal of an enzyme that regulates fatty
acid levels improves cognitive deficits in a mouse model of Alzheimer's disease.
A high-fat diet could promote the
development of Alzheimer's
A team of Université Laval researchers has shown that the main neurological markers for
Alzheimer's disease are exacerbated in the brains of mice fed a diet rich in animal fat
and poor in omega-3s. Details of the study—which suggests that diets typical of most
industrialized countries promote the development of Alzheimer's—are outlined in the
latest online edition of Neurobiology of Aging. To demonstrate this, the team led by
Frédéric Calon used a type of transgenic mice that produce two proteins found in the
brains of Alzheimer patients—tau proteins, which prevent proper neuron functioning,
and amyloid-beta, associated with the formation of senile plaques within the brains of
afflicted patients. The researchers fed transgenic and regular mice different diets for
nine months, after which they compared the effects on the animals' brains. The mice whose
diet was poor in omega-3s and rich in fat (60% of consumed calories) showed amyloid-beta
and tau protein concentrations respectively 8.7 and 1.5 times higher than the control
group mice, whose food contained 7 times less fat. The high-fat diet also reduced drebrin
protein levels in the brain, another characteristic of Alzheimer's disease.
"Metabolic changes induced by such a diet could affect the inflammatory response in
the brain," suggests study co-author Carl Julien to explain the link between fat
consumption and Alzheimer's. In most Western countries, diets rich in saturated fats and
poor in omega-3s are the norm. "Our findings lead us to believe that a diet
containing more omega-3s and less saturated fat could prevent the development of
Alzheimer's, at the very least among people genetically predisposed to the disease,"
comments Dr. Calon. "We cannot state with any certainty that what we have observed
among transgenic mice also occurs in humans, but there is no harm in eating less fat and
more omega-3s," concludes the researcher.
Mount Sinai researchers find new
Alzheimer's disease treatment promising
Researchers at Mount Sinai School of Medicine have found that a compound called NIC5-15,
might be a safe and effective treatment to stabilize cognitive performance in patients
with mild to moderate Alzheimer's disease. The two investigators, Giulio Maria Pasinetti,
M.D., Ph.D. , and Hillel Grossman, M.D., presented Phase IIA preliminary clinical findings
at the Alzheimer's Association 2009 International Conference on Alzheimer's Disease (ICAD)
in Vienna on Sunday, July 12. NIC5-15's potential to preserve cognitive performance will
be further evaluated in a Phase IIB clinical trial. Early evidence suggests that NIC5-15
is a safe and tolerable natural compound that may reduce the progression of Alzheimer's
disease-related dementia by preventing the formation of beta-amyloid plaque, a waxy
substance that accumulates between brain cells and impacts cognitive function. "With
Alzheimer's disease affecting 5.2 million Americans, another 5 million with early-state
disease, and nearly a half million new cases reported annually, treatments like NIC5-15
would make a significant difference in the lives of many Alzheimer's patients," said
Dr. Pasinetti, Professor of Psychiatry, Professor of Neuroscience and Professor of
Geriatrics and Adult Development, in the Department of Psychiatry at Mount Sinai School of
Medicine. "We are hopeful that the follow up clinical study will support this
preliminary evidence."
Results from trials of DHA in
Alzheimer's disease and age-related cognitive decline
Results from two large studies using DHA, an omega 3 fatty acid, were reported today at
the Alzheimer's Association 2009 International Conference on Alzheimer's Disease (ICAD
2009) in Vienna. One of the trials was conducted by the Alzheimer's Disease Cooperative
Study (ADCS) supported by the National Institute on Aging (NIA), and the second by Martek
Biosciences Corporation (Martek), the primary company that makes algal DHA for
supplementation. The NIA trial lasted 18 months and was conducted in people with mild to
moderate Alzheimer's. Martek's trial was six months, and the compound was tested in
healthy people to see its effect on "age related cognitive decline" (ARCD). Both
studies used Martek's algal DHA. The results of the ADCS trial show no evidence for
benefit in the studied population. The Martek trial showed a positive result on one test
of memory and learning, but that study was in healthy older adults, not people with
Alzheimer's or another dementia. The results need confirmation, as is standard scientific
practice. "These two studies – and other recent Alzheimer's therapy trials
– raise the possibility that treatments for Alzheimer's must be given very early in
the disease for them to be truly effective," said William Thies, PhD, Chief Medical
& Scientific Officer at the Alzheimer's Association. "For that to happen, we need
to get much better at early detection and diagnosis of Alzheimer's, in order to test
therapies at earlier stages of the disease and enable earlier intervention." Other
research studies from ICAD 2009 show advances made in biomarkers and early detection from
the Alzheimer's Disease Neuroimaging Initiative (ADNI), and also survey results from
doctors about the enablers and barriers they face in diagnosing people with Alzheimer's.
DHA (docosahexaenoic acid) is naturally found in the body in small amounts, and is the
most abundant omega 3 fatty acid in the brain. DHA oil is abundant in some marine
microalgae, which provide the DHA that makes fatty fish a good source of DHA. Dietary DHA
is also available in foods enriched with algal DHA or fish oils, and dietary supplements.
Previous animal studies and epidemiology in humans suggested that DHA may be beneficial in
people with Alzheimer's.
Of dozens of candidates potentially involved in increasing a person's risk for the most
common type of Alzheimer's disease that affects more than 5 million Americans over the age
of 65, one gene that keeps grabbing Johns Hopkins researchers' attention makes a protein
called neuroglobin. Adding to a growing body of evidence about the importance of this
protein for the health of the aging brain, researchers at the McKusick-Nathans Institute
of Genetic Medicine of the Johns Hopkins University School of Medicine canvassed the
genetic neighborhood of neuroglobin and, for the first time in a human population, linked
variation there with a risk for Alzheimer's. Ever so slight genetic variations between
individuals can and do influence the amounts of particular proteins that each specific
gene ultimately produces. In this case, the team has found that individuals with genetic
variations equating to less neuroglobin production have an increased risk for Alzheimer's.
"An intriguing part of this study was the high levels of neuroglobin that we found in
the Alzheimer's brain, which was exactly the opposite from what we expected," says
Dimitrios Avramopoulos, M.D., Ph.D., an associate professor in Hopkins' Institute of
Genetic Medicine and the Department of Psychiatry. Referring to data published in
Neurobiology of Aging, Avramopoulos explains that his team measured levels of gene product
in 56 different samples of human brain tissue: 30 from confirmed cases of Alzheimer's and
26 without brain disease. The scientists found that neuroglobin levels decreased with
advancing age, which, Avramopoulos points out, is consistent with risk of Alzheimer's
increasing with advancing age. They also found that levels of neuroglobin were lower in
women than in men, which is consistent with the fact that women have a slightly higher
risk of Alzheimer's. About two times as many patients in the general population with
Alzheimer's are women which, in part, can be attributed to the fact that women live longer
and therefore have more of a chance to get Alzheimer's. Having corrected for that
disparity, researchers have noted a slightly higher risk in women than in men. They were
surprised to find that neuroglobin levels were higher in the brain tissue from Alzheimer's
patients than that of the control group.
In a project involving the collaboration of several institutes, research scientists of the
Johannes Gutenberg University Mainz have succeeded in gaining further insight in the
functioning of endogenous mechanisms that protect against the development of Alzheimer's
disease. It was found that the activity of the enzyme ?-secretase is mainly responsible
for the protective effect. "In the past, we postulated that the enzyme ?-secretase
was involved in preventing the formation of cerebral plaques characteristic of Alzheimer's
disease and also enhanced cerebral functions, such as learning and memory," explained
Professor Falk Fahrenholz of the Institute of Biochemistry. His research group has been
working in cooperation with the Clinic of Psychiatry and Psychotherapy of the university's
Faculty of Medicine and the Central Animal Laboratory Facility (ZVTE) to discover the
mechanism for the beneficial effects of ?-secretase. The Journal of Alzheimer's Disease
(JAD) presents the results of this project in its February 2009 issue. ?-secretase is an
endogenous enzyme that is present in the nerve cells of the brain, where it is responsible
for the cleavage of an A? into A? domain. The result is a soluble protein fragment that
promotes the growth of nerve cells and thus prevents the development of cerebral
deterioration caused by A?. However, if the enzyme ?-secretase is active, a chain reaction
is initiated that subsequently results in the development A? initializing the cascade of
Alzheimer's disease through formation of A?. "You could say that ?-secretase is the
good enzyme, and ?-secretase the bad en-zyme," Fahrenholz commented. "We now
want to find out how to activate this 'good' enzyme or increase its concentrations in the
brain as a way of combating this disease."
CHEMICALS found in many fruits and vegetables, as well as tea, cocoa and red wine, could
protect the brain from Alzheimer's disease, a conference in Edinburgh heard today.
UCLA scientists identify how immune
cells may help predict Alzheimer's risk
What if you could test your risk for Alzheimer's disease much like your cholesterol levels
— through a simple blood test? UCLA scientists have discovered a way to measure the
amount of amyloid beta that is being absorbed by immune cells in the blood. Amyloid beta
forms the plaques considered the hallmark of Alzheimer's disease, and if the immune system
isn't adequately clearing amyloid beta, it may indicate Alzheimer's risk, according to the
researchers. MP Biomedicals LLC, a global life sciences and diagnostics company dedicated
to Alzheimer's disease research, has received an exclusive, worldwide license to
commercialize the UCLA technology and create a diagnostic blood test for public use to
screen for Alzheimer's risk. "Early diagnosis is the cornerstone of preventive
approaches to Alzheimer's disease," said Dr. Milan Fiala, lead author of the UCLA
study and a researcher at the David Geffen School of Medicine at UCLA and the Veterans
Affairs Greater Los Angeles Healthcare System. "We are pleased that the process we've
identified using immune cells to help predict Alzheimer's risk will be further developed
by MP Biomedicals." "We are excited by the opportunity to forward the UCLA
science in creating a cost-effective blood test to screen for Alzheimer's risk that could
be used in any hospital or lab," said Milan Panic, CEO of MP Biomedicals. Dr. Miodrag
Micic, vice president of research and development for MP Biomedicals, noted that other
blood tests for Alzheimer's diagnosis measure factors such as inflammation and infection,
which are also present in other diseases like atheroclerosis and may complicate the
interpretation of results.
New brain marker shows promise for
predicting future Alzheimer's disease
Duke University Medical Center researchers have used imaging technology to identify a new
marker that may help identify those at greatest risk for cognitive decline and the
development of Alzheimer's disease.
Gene scan of Alzheimer’s
families identifies four new suspect genes
The first family-based genome-wide association study in Alzheimer’s disease has
identified the sites of four novel genes that may significantly influence risk for the
most common late-onset form of the devastating neurological disorder. In their report in
the November 7 American Journal of Human Genetics, being released online today, a team led
by researchers from the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND)
describes how newly available technology is improving understanding of genetic mechanisms
underlying the disease. The study presents the first results of the Alzheimer’s
Genome Project supported by the Cure Alzheimer’s Fund and the National Institute of
Mental Health.
No benefit found from continuing
neuroleptic drugs in Alzheimer's patients
Results of a randomized trial published in PLoS Medicine show no benefit in cognitive or
neuropsychiatric outcomes from continuing neuroleptic drugs in patients with Alzheimer's
disease.
Research links diet to cognitive
decline and dementia
Research has shown convincing evidence that dietary patterns practiced during adulthood
are important contributors to age-related cognitive decline and dementia risk.
Research with grape polyphenols presented today at Neuroscience 2007 in San Diego shows
promise for maintaining long-term cognitive health. The researchers will now focus on
grape polyphenols and Alzheimer's disease at the newly established Center for Research in
Alternative and Complementary Medicine in Alzheimer's disease research at Mount Sinai
School of Medicine.
A Randomised, Blinded,
Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics
For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on
functional and cognitive status and by some measures improved functional and cognitive
status. Neuroleptics may have some value in the maintenance treatment of more severe
neuropsychiatric symptoms, but this possibility must be weighed against the unwanted
effects of therapy. The current study helps to inform a clinical management strategy for
current practice, but the considerable risks of maintenance therapy highlight the urgency
of further work to find, develop, and implement safer and more effective treatment
approaches for neuropsychiatric symptoms in people with AD.
Mitochondria play role in
pathogenesis of AD and estrogen-induced neuroprotection
As the major source of free radicals in cells, mitochondria contribute to the high levels
of oxidative stress believed to play a role in the pathogenesis of Alzheimer's disease.
Now a study demonstrates that estrogen reduces this oxidative stress caused by the
mitochondria while increasing the ability of the mitochondria to generate energy --
important since there is usually an energy deficit in the Alzheimer brain.
Lilly Touted Zyprexa for
Alzheimer's Knowing It Was Ineffective
Eli Lilly knew in 1995 that Zyprexa was ineffective for treating Alzheimer’s and
dementia in the elderly but promoted it for that purpose anyway, according to a lawsuit.
The suit also claims that each Zyprexa sales rep had a $10,000 budget that it used to pay
pharmacies and doctors for talking up off-label uses of Zyprexa.
Higher levels of aluminum in drinking water appear to increase people's risk of developing
Alzheimer's disease, whereas higher levels of silica appear to decrease the risk,
according to French investigators.
If you’re middle-aged, get divorced and live alone, you triple your chances of
Alzheimer’s according to research that looked at the brain health of more than 2,000
Finns.
Mortality With Antipsychotic Use in
Alzheimer Disease
Mortality in elderly patients with dementia markedly and progressively increases with
extended use of antipsychotics, according to the first long-term controlled study of risk
in this population. Earlier evidence of this risk was from short-term trials not exceeding
14 weeks.
Mitochondria Could Be a Target for
Therapeutic Strategy for Alzheimer’s Disease Patients
A study in the edition of Nature Medicine describes the function and interaction of a
critical molecule involved in cell death in Alzheimer’s disease patients. These new
findings reveal that blocking this molecule, called Cyclophilin D (CypD), and development
of surrounding mitochondrial targets may be viable therapeutic strategies for the
prevention and treatment of Alzheimer’s disease, according to Shi Du Yan, Ph.D.,
professor of clinical pathology in the Department's of Pathology and Surgery and in the
Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia
University Medical Center, who led the multi-center research. This paper strengthens the
concept that mitochondrial permeability pores may be central in mitochondrial and neuronal
malfunction relevant to Alzheimer disease. Dr. Yan and her colleagues offer new insights
into the mechanism underlying amyloid beta (A?)-mediated mitochondrial stress through an
interaction with CypD, which is linked to synaptic plasticity and learning/memory.
Importantly, these findings may help explain the mechanism of action of a medication
already in use in clinical trials.
alzheimer
Protecting neurons could halt Alzheimer's, Parkinson's diseases
Researchers at Southern Methodist University (SMU) and The University of Texas at Dallas
(UTD) have identified a group of chemical compounds that slow the degeneration of neurons,
a condition behind old-age diseases like Alzheimer's, Parkinson's and amyotrophic lateral
sclerosis (ALS). Their findings are featured in the November 2008 edition of Experimental
Biology and Medicine. SMU Chemistry Professor Edward R. Biehl and UTD Biology Professor
Santosh D'Mello teamed to test 45 chemical compounds. Four were found to be the most
potent protectors of neurons, the cells that are core components of the human brain,
spinal cord and peripheral nerves.The most common cause of neurodegenerative disease is
aging. Current medications only alleviate the symptoms but do not affect the underlying
cause – degeneration of neurons. The identification of compounds that inhibit
neuronal death is of urgent and critical importance.
alzheimer
Dietary acrylamide may play a role in Alzheimer’s, researchers theorize
Scientists have known for years that acrylamide is capable of causing nerve damage in
humans, including muscle weakness and impaired muscle coordination, particularly from
industrial exposure to large levels of the chemical. Now, new laboratory studies suggest
that chronic dietary exposure to the chemical is capable of damaging nerve cells in the
brain and could potentially play a role in the development of neurodegenerative disease,
including Alzheimer’s, according to Richard LoPachin, Jr., Ph.D., a neurotoxicologist
with Albert Einstein College of Medicine in New York. He notes that acrylamide is
structurally similar to acrolein, a chemical found in increased levels in brains of
patients with Alzheimer’s and other neurodegenerative diseases. Studies in humans are
warranted, the researcher says.
alzheimer
Discovery supports theory of Alzheimer's disease as form of diabetes
Insulin may be as important for the mind as it is for the body. Recent research has raised
the possibility that Alzheimer's memory loss could be due to a novel third form of
diabetes. Scientists at Northwestern University have discovered why brain insulin
signaling would stop working in Alzheimer's disease. They have shown that a toxic protein
found in the brains of individuals with Alzheimer's removes insulin receptors from nerve
cells, rendering those neurons insulin-resistant.
A vitamin found in meat, fish and potatoes may help protect the brain from Alzheimer's
disease - and even boost memory in healthy people.US researchers found vitamin B3 lowered
levels of a protein linked to Alzheimer's damage in mice.
alzheimer
Redox-active iron is a sensor of cognitive impairment associated with Alzheimer's disease
An innovative discovery has been reported that highlights the problems that oxidative
stress resulting from iron cumulated in the human brain can generate in relation with the
pathogenesis of Alzheimer's disease, the brain disorder affecting almost 30 million
throughout the world. The results of research appeared recently in Volume 13, Issue 2 of
the prestigious Journal of Alzheimer's Disease.
A special type of collagen may help
protect the brain against Alzheimer's disease
Scientists from the Gladstone Institute of Neurological Disease (GIND), UCSF, and Stanford
have discovered that a certain type of collagen, collagen VI, protects brain cells against
amyloid-beta (A? ) proteins, which are widely thought to cause Alzheimer's disease (AD).
While the functions of collagens in cartilage and muscle are well established, before this
study it was unknown that collagen VI is made by neurons in the brain and that it can
fulfill important neuroprotective functions. The team of investigators led by GIND
director Lennart Mucke, MD, reported in a recent edition of the journal Nature
Neuroscience, that collagen VI is increased in brain tissues of Alzheimer's patients.
"We first noticed the increase in collagen VI in the brain of AD mouse models, which
inspired us to look for it in the human condition and to define its role in the
disease," said Dr. Mucke. The Gladstone team had profiled changes in gene expression
using DNA microarrays, which provides an unbiased method for identifying key biological
pathways. By comparing all of the genes that are active in disease and normal tissue, one
can get valuable information on new pathways and potential therapeutic targets. The
researchers looked at the dentate gyrus, a specific area of the brain that is critical to
memory and particularly vulnerable in AD, and compared the genes that were turned on and
off in normal mice and a mouse model of AD. This analysis revealed the striking increase
in collagen VI in the brains of mice that model AD. Building on this initial finding, the
team examined brain tissue from AD patients and normal non-demented humans and found that
collagen VI expression was also higher in the AD patients. They further discovered that
the cellular source of the collagen VI in the brain was neurons, the very cells that the
disease attacks and that we all need to think and remember.
Alzheimer's molecule is a smart
speed bump on the nerve-cell transport highway
Researchers at the University of Pennsylvania School of Medicine discovered that proteins
carrying chemical cargo in nerve cells react differently when exposed to the tau protein,
which plays an important role in Alzheimer's disease.
Evidence found for genes that
affect risk of developing Alzheimer's disease
Through one of the largest studies yet of Alzheimer's disease patients and their brothers,
sisters, and children, researchers at Mayo Clinic Jacksonville have found strong evidence
that genes other than the well-known susceptibility risk factor APOE4 influence who is at
risk for developing the neurodegenerative disease later in life.
Altering brain's lipid metabolism
reduces Alzheimer's plaques in mice
Increasing levels of a protein that helps the brain use cholesterol may slow the
development of Alzheimer's disease changes in the brain, according to researchers studying
a mouse model of the disease at Washington University School of Medicine in St. Louis.
In a paper published in the latest edition of the Journal of Alzheimer’s Disease,
folate is shown to be beneficial in the screening system. Lead author, CSIRO’s Dr Ian
Macreadie says folate is already well known to have a protective effect against
Alzheimer’s disease which is believed to be caused by the loss of neurons in the
brain due to a process whereby toxic multimers of a small protein called A? are formed.
“However, a team of scientists working within CSIRO’s Preventative Health
Flagship has discovered a rapid screening system to identify inhibitors of this process.
Compounds that inhibit the formation of the toxic multimers may lead to the prevention or
delay of the disease,” Dr Macreadie says. “Although many other research groups
and drug companies around the world are trying to find compounds that act in the same way,
the advance by the Flagship team involves using live yeast with the A? protein fused to a
green fluorescent protein that comes from jellyfish.
Researchers link metal ions to
neurodegenerative disease
Researchers have defined for the first time how metal ions bind to amyloid fibrils in the
brain in a way that appears toxic to neurons. Amyloid fibrils are linked to the
development of neurodegenerative diseases such as Alzheimer's, Parkinson's and
Creutzfeldt-Jakob. Although metal ions, most notably copper, can bind to amyloid in
several specific ways, the researchers found that only one way appears toxic.
MRI brain scans accurate in early
diagnosis of Alzheimer's disease
MRI scans that detect shrinkage in specific regions of the mid-brain attacked by
Alzheimer’s disease accurately diagnose the neurodegenerative disease, even before
symptoms interfere with daily function, a study by the Florida Alzheimer’s Disease
Research Center (ADRC) in Miami and Tampa found. The study, reported earlier this month in
the journal Neurology, adds to a growing body of evidence indicating MRI brain scans
provide valuable diagnostic information about Alzheimer’s disease. The findings are
important in light of many new disease-modifying drugs in trials -- treatments that may
prevent mild memory loss from advancing to full-blown dementia if administered early
enough. "We advocate, based on these findings, that the criteria for the diagnosis of
Alzheimer’s disease should include MRI scans,” said the study’s lead author
Ranjan Duara, MD, medical director of the Wien Center for Alzheimer’s Disease and
Memory Disorders at Mount Sinai Medical Center who is affiliated with the University of
Miami Miller School of Medicine and University of South Florida College of Medicine.
“By incorporating MRIs into the assessment of patients with memory problems, early
diagnosis can be standardized and done far more accurately.”
Altering Brain's Lipid Metabolism
Reduces Alzheimer's Plaques In Mice
Increasing levels of a protein that helps the brain use cholesterol may slow the
development of Alzheimer's disease changes in the brain, according to researchers studying
a mouse model of the disease at Washington University School of Medicine in St. Louis.
Tel Aviv University researcher goes
'through the nose' to delay onset of Alzheimer's disease
Tel Aviv University researcher goes 'through the nose' to delay onset of Alzheimer's
diseaseNew drug candidate dissolves plaques associated with Alzheimer's and other
neurological diseases.
Calpain inhibitors never forget -
Improving memory in Alzheimer's disease mice
Overactivation of proteins known as calpains, which are involved in memory formation, has
been linked to Alzheimer disease. Ottavio Arancio and colleagues, at Columbia University,
New York, have now shown that two different drugs that inhibit calpains can improve memory
in a mouse model of Alzheimer disease (APP/PS1 mice), leading them to suggest drugs that
target calpains might stop or slow down the memory loss that occurs as Alzheimer disease
progresses.It is thought that dysfunctional signaling between nerve cells contributes to
the impaired cognition experienced by individuals with Alzheimer disease. In the study,
analysis of cells and tissue slices from APP/PS1 mice, specifically cells from the part of
the brain known as the hippocampus and hippocampal slices, indicated that exposure to
calpain inhibitors restored signaling between nerve cells to normal. The authors therefore
suggest that calpain inhibitors improve memory in APP/PS1 mice because they reestablish
normal signaling between nerve cells.
Two cardiovascular proteins pose a
double whammy in Alzheimer's
Researchers have found that two proteins which work in tandem in the brain's blood vessels
present a double whammy in Alzheimer's disease. Not only do the proteins lessen blood flow
in the brain, but they also reduce the rate at which the brain is able to remove amyloid
beta, the protein that builds up in toxic quantities in the brains of patients with the
disease. The work, described in a paper published online Dec. 21 in the journal Nature
Cell Biology, provides hard evidence directly linking two processes thought to be at play
in Alzheimer's disease: reduction in blood flow and the buildup of toxic amyloid beta. The
research makes the interaction between the two proteins a seductive target for researchers
seeking to address both issues. Scientists were surprised at the finding, which puts two
proteins known for their role in the cardiovascular system front and center in the
development of Alzheimer's disease. "This is quite unexpected," said Berislav
Zlokovic, M.D., Ph.D., a neuroscientist and a senior author of the study. "On the
other hand, both of these processes are mediated by the smooth muscle cells along blood
vessel walls, and we know that those are seriously compromised in patients with
Alzheimer's disease, so perhaps we shouldn't be completely surprised." The new
findings are the result of a seven-year collaboration between two laboratories. Zlokovic
heads the Center for Neurodegenerative and Vascular Brain Disorders, looking at molecular
roots of diseases like Alzheimer's. Several years ago, after he found that several genes
well known to cardiovascular researchers seemed to be especially affected in Alzheimer's
patients, he turned to Joseph Miano, Ph.D. to help analyze the findings. Miano is interim
director of Aab Cardiovascular Research Institute and associate professor of Medicine, and
he is senior co-author of the new study.
Grapeseedextract as effective as
red wine in preventing amyloid beta plaque build up
A compound found in grape seed extract reduces plaque formation and resulting cognitive
impairment in an animal model of Alzheimer’s disease, new research shows. The study
appears in the June 18 issue of The Journal of Neuroscience. Lead study author Giulio
Pasinetti, MD, PhD, of Mount Sinai School of Medicine and colleagues found that the grape
seed extract prevents amyloid beta accumulation in cells, suggesting that it may block the
formation of plaques. In Alzheimer’s disease, amyloid beta accumulates to form toxic
plaques that disrupt normal brain function. The researchers tested a grape seed
polyphenolic extract product sold as MegaNatural-AZ, made by Polyphenolics, which in part
supported the study. Polyphenolic compounds are antioxidants naturally found in wine, tea,
chocolate, and some fruits and vegetables. To determine whether the extract could mitigate
the effects of Alzheimer’s disease, the researchers used mice genetically modified to
develop a condition similar to Alzheimer’s disease. They exposed pre-symptomatic
“Alzheimer’s mice” to the extract or placebo daily for five months. The
daily dose of the polyphenolic extract was equivalent to the average amount of
polyphenolics consumed by a person on a daily basis.
Brain starvation as we age appears
to trigger Alzheimer's
A slow, chronic starvation of the brain as we age appears to be one of the major triggers
of a biochemical process that causes some forms of Alzheimer's disease. A new study from
Northwestern University's Feinberg School of Medicine has found when the brain doesn't get
enough sugar glucose -- as might occur when cardiovascular disease restricts blood flow in
arteries to the brain -- a process is launched that ultimately produces the sticky clumps
of protein that appear to be a cause of Alzheimer's. Robert Vassar, lead author,
discovered a key brain protein is altered when the brain has a deficient supply of energy.
The altered protein, called elF2alpha, increases the production of an enzyme that, in
turn, flips a switch to produce the sticky protein clumps. Vassar worked with human and
mice brains in his research.
Draining away brain's toxic protein
to stop Alzheimer's
Scientists have shown how the body's natural way of ridding the body of the toxic protein
amyloid-beta is flawed in people with the disease. Then the team demonstrated an
experimental method in mice to fix the process, dramatically reducing the levels of the
toxic protein in the brain and halting symptoms.
Mechanistic Link Discovered between
Calcium Signaling and Alzheimer Gene
Scientists from the Institute for Aging and Alzheimer’s Disease Research (IAADR)
based in Fort Worth, Texas, have discovered a molecular mechanism that links the activity
of a crucial protein involved in Alzheimer’s disease with a fundamental signaling
process in nerve cells. Published online in The International Journal of Biochemistry
& Cell Biology , the research was funded by the National Institute on Aging (NIA),
part of the National Institutes of Health (NIH) and the Alzheimer’s Association. The
discovery builds on previous research from several NIA-funded laboratories that identified
mutations in the Alzheimer’s disease related gene presenilin-1 as the cause of
impaired activity and reduced health of nerve cell in the brain. The study’s lead
investigator, Peter Koulen, Ph.D., of the IAADR at the University of North Texas Health
Science Center had two major goals when he initiated the study in 2003: to identify the
role of normal, so-called wild-type presenilin-1 in regulating neuronal function, and to
reach the mechanism that drives this function. This appeared to be of particular relevance
because only a small portion of Alzheimer’s disease sufferers carries such mutations
(often called familial Alzheimer’s disease), while the majority of patients have
sporadic Alzheimer’s disease, in which no apparent direct genetic changes have been
identified.
2 proteins in cardiovascular system
pose a double whammy in Alzheimer’s
A new study has identified two proteins that cause patients with Alzheimer’s disease
to face the double whammy of a lessened blood flow in the brain and reduced rate of
brain’s ability to remove amyloid beta. The researchers behind the study have
revealed that the two proteins work in tandem in the brain’s blood vessels.
Brain ‘trick’ offers
treatment hope for Alzheimer’s
Scientists in the UK and Canada have made a significant step forward in the search for new
drugs to treat Alzheimer’s disease. An ageing population means that
neurodegeneration, such as Alzheimer’s disease, is one of the major health problems
in the developed world. But researchers at the University of York and Simon Fraser
University in Burnaby, British Columbia, have designed an enzyme inhibitor which could
‘trick’ the brain and so help to halt neurodegeneration.
Study identifies toxic key to
Alzheimer’s disease memory loss
The team of Irish and international researchers have identified that the accumulation of a
particular protein (called amyloid ß-protein - Aß) in the brain initiates
Alzheimer’s disease and that it directly alters the structure and function of brain
cells. The findings place a significant emphasis on the development of new therapeutic
strategies targeted at the reduction of the formation of Aß as opposed to the reduction
of the plaque burden associated with the disease.
Columbia researchers identify brain
network that may help prevent or slow Alzheimer's
Columbia University Medical Center researchers, led by principal investigator Yaakov
Stern, Ph.D., a professor at the Taub Institute for the Research on Alzheimer's Disease
and the Aging Brain, have identified a brain network within the frontal lobe that is
associated with cognitive reserve, the process that allows individuals to maintain
function despite brain function decline due to aging or Alzheimer's disease.
Splenic ellipsoids might be
significant in the early development of AA amyloidosis
During the course of her PhD studies, Randi Sørby demonstrated that ellipsoids, small
filtering units for blood in the spleen, might be significant in the development of AA
amyloidosis. AA amyloidosis is a potential complication of chronic inflammation or
infection, for example, rheumatoid arthritis and tuberculosis, and is characterised by
systematic deposition of protein fibrils in the tissues of organs such as the spleen and
liver. Similar deposition, but of other proteins, also occurs in diseases such as
Alzheimer's disease, Parkinson’s disease, and prion-associated disease ("mad cow
disease"). In her thesis, Randi Sørby used experimental amyloidosis in the mink as a
model to study how amyloid deposition arises in different parts of the spleen. This model
was chosen because the mink has especially well-developed ellipsoids, which are lacking in
the more commonly-used experimental animals such as mouse and rat, but which are found in
most other mammals, including man. Studies have shown that ellipsoids are central
structures in amyloid deposition and that they play an early role in the development of
the disease.
Back in 2004, I wrote three columns (when I was at The Wall Street Journal) on how one
particular theory of what causes this awful disease—and therefore the best approach
for treating it—has had the field in a headlock, censoring competing theories. That
closed-mindedness, I quoted scientists as saying, had a lot to do with why there is not
only no cure or preventive for Alzheimer’s, but not even a treatment that slows down
the inexorable cognitive decline.
Antipsychotics Bring Little
Long-Term Benefit in Alzheimer's
At week 12, investigators found no significant differences between patients treated with
an antipsychotic medication and those treated with placebo in scores on measures of
cognition, function, and quality of life.
Research on the mechanisms involved in neurodegenerative diseases such as Alzheimer's,
stroke, dementia, Parkinson's and multiple sclerosis, to name a few, has taken a step
forward thanks to the work of biological sciences Ph.D. student Sonia Do Carmo, supervised
by Professor Éric Rassart of the Université du Québec à Montreal (UQAM) Biological
Sciences Department, in collaboration with researchers at the Armand-Frappier Institute
and the University of Valladolid in Spain. Do Carmo and her collaborators have
successfully demonstrated the protective and reparative role of apolipoprotein D, or ApoD,
in neurodegenerative diseases. Their discovery suggests interesting avenues for preventing
and slowing the progression of this type of illness. These studies were inspired by work
done ten years ago by Professor Rassart's team, who then discovered increased levels of
ApoD in the brains of people with several types of neurodegenerative disorders, including
Alzheimer's. The team hypothesized that this protein might play a protective and
restorative role but were unable to demonstrate this at the time.
Researchers have found that a technique used to visualize amyloid fibers in the laboratory
might have the potential to destroy them in the clinic. The technique involves zapping the
fluorescently-tagged fibers with a laser, which can inhibit their growth and degrade them.
This study, appearing in this week's JBC, may offer a non-drug alternative to treat
amyloid-based disorders like Alzheimer, Parkinson, and Huntington diseases. Yuji Goto and
colleagues had been studying amyloids, dense tangles of protein, to better understand how
they form. In an effort to view amyloid formation under a microscope in real-time, they
added an amyloid specific dye called thioflavin T (ThT) to the tangles and then hit it
with a laser beam to induce fluorescence. Surprisingly, they found that under the right
conditions, the laser could actually stop fiber growth and even degrade the amyloids.
Collagen VI may help protect the
brain against Alzheimer's disease
Scientists from the Gladstone Institute of Neurological Disease (GIND), UCSF, and Stanford
have discovered that a certain type of collagen, collagen VI, protects brain cells against
amyloid-beta (A?) proteins, which are widely thought to cause Alzheimer's disease (AD).
While the functions of collagens in cartilage and muscle are well established, before this
study it was unknown that collagen VI is made by neurons in the brain and that it can
fulfill important neuroprotective functions. The team of investigators led by GIND
director Lennart Mucke, MD, reported in the current edition of the journal Nature
Neuroscience, that collagen VI is increased in brain tissues of Alzheimer's
patients."We first noticed the increase in collagen VI in the brain of AD mouse
models, which inspired us to look for it in the human condition and to define its role in
the disease," said Dr. Mucke. The Gladstone team had profiled changes in gene
expression using DNA microarrays, which provides an unbiased method for identifying key
biological pathways. By comparing all of the genes that are active in disease and normal
tissue, one can get valuable information on new pathways and potential therapeutic
targets. The researchers looked at the dentate gyrus, a specific area of the brain that is
critical to memory and particularly vulnerable in AD, and compared the genes that were
turned on and off in normal mice and a mouse model of AD. This analysis revealed the
striking increase in collagen VI in the brains of mice that model AD.
Antipsychotic drugs double risk of
death among Alzheimer’s patients
New research into the effects of antipsychotic drugs commonly prescribed to
Alzheimer’s patients concludes that the medication nearly doubles risk of death over
three years. The study, funded by the Alzheimer’s Research Trust, was led by Prof
Clive Ballard’s King’s College London team and is published in Lancet Neurology
on 9 January. The study involved 165 Alzheimer’s patients in care homes who were
being prescribed antipsychotics. 83 continued treatment and the remaining 82 had it
withdrawn and were instead given oral placebos.
High stress levels may contribute to memory loss among people at risk for developing
Alzheimer's disease. The å4 variant of the apolipoprotein E (APOE) gene contributes to
the risk for memory loss related to Alzheimer's disease.
Ionophore reverses Alzheimer's
within days in mouse models
Scientists report a remarkable improvement in Alzheimer's transgenic mice following
treatment with a new drug. The study, published by Cell Press in the July 10th issue of
the journal Neuron, provides the first demonstration that an ionophore, a compound that
transports metal ions across cell membranes, can elicit rapid and pronounced improvement
in neuropathology and cognitive function in mouse models of Alzheimer's Disease (AD).
Recent research has implicated dysregulation of metal ions in the brain, particularly
copper and zinc, in the pathogenesis of AD and the damaging accumulation of amyloid beta
(A?) protein that is characteristic of this devastating disease. The ionophore clioquinol
(CQ), an 8-hydroxyquinoline, has been shown to increase intracellular copper and zinc
levels and decrease A? levels in cultured cells and in the brains of transgenic (Tg) AD
mice. However, further studies in mice and humans demonstrated that brain entry of CQ was
quite limited.
A dietary cocktail that includes a type of omega-3 fatty acid can improve memory and
learning in gerbils, according to the latest study from MIT researchers that points to a
possible beverage-based treatment for Alzheimer's and other brain diseases.
Mayo Clinic Researchers Find that
Variants in a Gene on the X Chromosome are Associated with Increased Susceptibility to
Alzheimer's Disease
Researchers at Mayo Clinic have discovered the first gender-linked susceptibility gene for
late-onset Alzheimer's disease.In the Jan. 11 online edition of Nature Genetics, they
report the results of their two-stage genome-wide association study of patients with
Alzheimer's disease. The research showed that women who inherited two copies of a variant
in the PCDH11X gene, found on the X chromosome, are at considerably greater risk of
developing Alzheimer's disease. Women with a variant on one of their two X chromosomes
also had some increase in risk, as did men with the variant on their single X chromosome,
but these effects were weaker than inheriting two variants.
Calcium may be the key to
understanding Alzheimer's disease
Researchers at the University of Pennsylvania School of Medicine have shown that mutations
in two proteins associated with familial Alzheimer's disease disrupt the flow of calcium
ions within neurons. The two proteins, called PS1 and PS2 (presenilin 1 and 2), interact
with a calcium release channel in an intracellular cell compartment.
Possible Alzheimer's Disease Marker
Discovered in Rare Genotype
Researchers at Banner Health's Sun Health Research Institute have uncovered evidence that
Alzheimer's disease (AD) may be clinically confirmed in patients with apolipoprotein E2
homozygote. The results of their study are published in the January 2009 issue of the
Journal of Alzheimer's Disease.
Apolipoprotein E2 homozygote has been associated with a protective effect against AD and
contributes to delaying the onset of symptoms. However previously, no significant data had
pointed to clinically confirmed AD in persons with apolipoprotein E2 homozygote. The
reverse is true of apolipoprotein E4. Previous studies have confirmed that apolipoprotein
E4 is a predictive risk factor for AD and indicates an increased genetic risk of AD.
Clinical confirmation of the apolipoprotein E2 homozygote Alzheimer's disease finding in
this study was confirmed by MRI, PET and neuropsychological evaluation and testing. AD
pathology is yet to be determined and will occur at post mortem.
Early study reveals promising
Alzheimer's disease treatment
A drug once approved as an antihistamine in Russia improved thinking processes and the
ability to function in patients with Alzheimer's disease in a study conducted there, said
an expert at Baylor College of Medicine in Houston. The findings are published in the
current issue of the journal The Lancet.
New step in DNA damage response in
neurons discovered
Researchers have identified a biochemical switch required for nerve cells to respond to
DNA damage. The finding, scheduled for advance online publication in Nature Cell Biology,
illuminates a connection between proteins involved in neurodegenerative disease and in
cells' response to DNA damage. Most children with the inherited disease ataxia
telangiectasia are wheelchair-bound by age 10 because of neurological problems. Patients
also have weakened immune systems and more frequent leukemias, and are more sensitive to
radiation. The underlying problem comes from mutations in the ATM (ataxia telangiectasia
mutated) gene, which encodes an enzyme that controls cells' response to and repair of DNA
damage. ATM can be turned on experimentally by treating cells with chemicals that damage
DNA. After other proteins in the cell detected broken DNA needing repair, scientists had
thought that the ATM protein could activate itself directly. Emory researchers have shown
that an additional step is necessary first. "In neurons that are not dividing
anymore, we now know that another regulator is involved: Cdk5," says Zixu Mao, MD,
PhD, associate professor of pharmacology and neurology at Emory University School of
Medicine. Working with postdoctoral fellows Bo Tian, PhD and Qian Yang, PhD, Mao found
that the Cdk5 protein must activate ATM before ATM can do its job in neurons. The results
support the idea that Cdk5 may be a potential drug target. Cdk5 contributes to normal
brain development, and aberrant Cdk5 activity is known to be involved in the death of
neurons in several neurodegenerative diseases, including Alzheimer's, Parkinson's and
amyotrophic lateral sclerosis.
Scientists demonstrate means of
reducing Alzheimer's-like plaques in fly brain
Neuroscientists at Cold Spring Harbor Laboratory are part of a collaboration that has
succeeded in demonstrating that overexpression of an enzyme in the brain can reduce
telltale deposits causally linked with Alzheimer's disease.
Video released of rapid Alzheimer's
improvement after new immune-based treatment
New research into the treatment of Alzheimer's disease reports improvement in language
abilities using a novel immune-based approach. A video accompanying the research,
published today in the open access journal BMC Neurology, documents rapid language
improvement within minutes of using this new treatment.
The Ocean Water properties as supplemental food are giving excellent results in the sports
field and in other areas of human activity, for which we hope that it will be very
positive for Alzheimer patients.
In furthering the steps toward that goal, UCLA associate professor of neurology John
Ringman and his colleagues confirm in the current issue of the journal Neurology that
during Alzheimer's earliest stages, levels of specific proteins in the blood and spinal
fluid begin to drop as the disease progresses, making them potentially useful as
biomarkers to identify and track progression long before symptoms appear.
New study provides further evidence
that apple juice can delay onset of Alzheimer's disease
A growing body of evidence demonstrates that we can take steps to delay age-related
cognitive decline, including in some cases that which accompanies Alzheimer's disease,
according to a study published in the January 2009 issue of the Journal of Alzheimer's
Disease. Thomas B. Shea, PhD, of the Center for Cellular Neurobiology; Neurodegeneration
Research University of Massachusetts, Lowell and his research team have carried out a
number of laboratory studies demonstrating that drinking apple juice helped mice perform
better than normal in maze trials, and prevented the decline in performance that was
otherwise observed as these mice aged. In the most recent study Shea and his team
demonstrated that mice receiving the human equivalent of 2 glasses of apple juice per day
for 1 month produced less of a small protein fragment, called "beta-amyloid"
that is responsible for forming the "senile plaques" that are commonly found in
brains of individuals suffering from Alzheimer's disease.
An experimental helmet is being tested by scientists as a treatment for Alzheimer's
disease. It delivers low levels of infra-red light, which researchers at the University of
Sunderland, believe may stimulate the growth of brain cells.
New study finds healthy children of
Alzheimer patients show early brain changes
Medical College of Wisconsin researchers in Milwaukee have reported that children of
Alzheimer's patients who are carriers of a genetic risk factor for Alzheimer's disease
have neurological changes that are detectable long before clinical symptoms may appear.
A team of UIC chemists has characterized the molecular structure of the intermediate stage
of plaque-forming amyloid fibrils, believed to cause Alzheimer's disease. The finding may
lead to new drug targets for this and other amyloid diseases, such as Parkinson's and
Creutzfeldt-Jakob.
Thyroid Hormone May Boost Women's
Alzheimer's Risk
High or low levels of the hormone thyrotropin may be associated with an increased risk of
Alzheimer's disease in women. Thyrotropin affects thyroid gland function and thyroid
hormone levels.
Researchers Find Use of Angiotensin
Receptor Blockers are Associated with Lower Incidence, Progression of Alzheimer’s
Disease
Researchers at Boston University School of Medicine (BUSM) have, for the first time, found
that angiotensin receptor blockers (ARBs)—a particular class of anti-hypertensive
medicines—are associated with a striking decrease in the occurrence and progression
of dementia. Data from this study will be presented this weekend (July 27) at the 2008
International Conference on Alzheimer’s disease in Chicago.
Consumption of fruits may reduce
the risk of Alzheimer's disease
Apples, bananas, and oranges are the most common fruits in both Western and Asian diets,
and are important sources of vitamins, minerals, and fiber. A new study in the Journal of
Food Science explores the additional health benefits of these fruits and reveals they also
protect against neurodegenerative diseases, including Alzheimer's disease.
Alzheimer's disease patients show
improvement in trial of new drug
A new drug has been shown to improve the brain function of people with early stage
Alzheimer's disease and reduce a key protein associated with the disease in the spinal
fluid, in a small study published today in the journal Lancet Neurology and presented at
the 2008 Alzheimer's Association International Conference on Alzheimer's Disease.
Sugary beverages increase risk of
Alzheimer's disease
Drinking sugary beverages like soda may increase risk of Alzheimer's disease, according to
a new study published in the Dec. 14, 2007 issue of Journal of Biological Chemistry.
Signs of Alzheimer's disease may be
present decades before diagnosis
Scientists from the University of South Florida and the University of Kentucky report that
people who develop Alzheimer's disease may show signs of this illness many decades earlier
in life, including compromised educational achievement.
PET scans may help assess presence
of brain plaques related to Alzheimer's disease
A type of positron emission tomography (PET) scanning may be useful in a non-invasive
assessment of the formation of Alzheimer’s disease–related plaques in the brain,
according to small study posted online today that will appear in the October 2008 print
issue of Archives of Neurology, one of the JAMA/Archives journals. Plaques in the brain
made of beta-amyloid and other compounds are considered hallmarks of the development of
Alzheimer’s disease, according to background information in the article. Currently,
the only reliable way to assess the aggregation of these compounds in the brain is through
analyzing brain tissue samples obtained during life or autopsy after death—“a
major methodological obstacle considering clinical drug trials of early Alzheimer’s
disease,” the authors note.
Protein aggregation is a process in which identical proteins self-associate into
imperfectly ordered macroscopic entities. Such aggregates are generally classified as
amorphous, lacking any long-range order, or highly ordered fibrils. Protein fibrils can be
composed of native globular molecules, such as the hemoglobin molecules in sickle-cell
fibrils, or can be reorganized ?-sheet–rich aggregates, termed amyloid-like fibrils.
Amyloid fibrils are associated with several pathological conditions in humans, including
Alzheimer disease and diabetes type II. We studied the structure of bacterial inclusion
bodies, which have been believed to belong to the amorphous class of aggregates. We
demonstrate that all three in vivo-derived inclusion bodies studied are amyloid-like and
comprised of amino-acid sequence-specific cross-? structure. These findings suggest that
inclusion bodies are structured, that amyloid formation is an omnipresent process both in
eukaryotes and prokaryotes, and that amino acid sequences evolve to avoid the amyloid
conformation.
Iron banded worms drying out of
blood could be linked to Parkinson's and Alzheimer's
Researchers at the University of Warwick and the Indian Institute of Technology Kanpur
have discovered that the mechanism that we rely on to transport iron safely through our
blood can collapse into a state which grows long worm-like "fibrils" banded by
lines of iron rust. This process could provide the first insight into how iron gets
deposited in the brain to cause some forms of Parkinson's & Alzheimer's and
Huntington's diseases.
Physical frailty may be linked to
Alzheimer's disease
Physical frailty, which is common in older persons, may be related to Alzheimer's disease
pathology, according to a study published in the Aug. 12, 2008, issue of Neurology, the
medical journal of the American Academy of Neurology.
Preventing Alzheimer's from developing is a goal of Raphael Kopan, Ph.D., professor of
molecular biology and pharmacology at the Washington University in St. Louis School of
Medicine. The moss plant studied in the laboratory of Ralph S. Quatrano, Ph.D., Spencer T.
Olin Professor of biology, might inch Kopan toward that goal. Through collaboration, the
researchers have found that a gene in moss is also structurally conserved in AD and has
similar functions.
UCLA researchers report that omega-3 fatty acid docosahexaenoic acid, found in fish oil,
increases the production of LR11, a protein that is found at reduced levels in Alzheimer's
patients and which is known to destroy the the "plaques" associated with the
disease.
Tampa Researchers Find Caffeine
Eases Alzheimer's Effects
Given the already widespread use and acceptance of coffee in moderate amounts," they
wrote, "long-term coffee intake could be a viable strategy" for reducing the
risk of Alzheimer's disease.
People with Alzheimer's disease eat less nutritiously than their peers without dementia,
even in the early stages of the disease, new research from Canada shows.
Scientists call it the "French paradox" — a society that, despite consuming
food high in cholesterol and saturated fats, has long had low death rates from heart
disease. Research has suggested it is the red wine consumed with all that fatty food that
may be beneficial — and not only for cardiovascular health but in warding off certain
tumors and even Alzheimer's disease. Now, Alzheimer's researchers at UCLA, in
collaboration with Mt. Sinai School of Medicine in New York, have discovered how red wine
may reduce the incidence of the disease. Reporting in the Nov. 21 issue of the Journal of
Biological Chemistry, David Teplow, a UCLA professor of neurology, and colleagues show how
naturally occurring compounds in red wine called polyphenols block the formation of
proteins that build the toxic plaques thought to destroy brain cells, and further, how
they reduce the toxicity of existing plaques, thus reducing cognitive deterioration.
Polyphenols comprise a chemical class with more than 8,000 members, many of which are
found in high concentrations in wine, tea, nuts, berries, cocoa and various plants. Past
research has suggested that such polyphenols may inhibit or prevent the buildup of toxic
fibers composed primarily of two proteins — Aß40 and Aß42 — that deposit in
the brain and form the plaques which have long been associated with Alzheimer's. Until
now, however, no one understood the mechanics of how polyphenols worked.
Mice that were fed a diet rich in fat, sugar and cholesterol for nine months developed a
preliminary stage of the morbid irregularities that form in the brains of Alzheimer’s
patients. The study results, published in a doctoral thesis from the Swedish medical
university Karolinska Institutet (KI), give some indications of how this difficult to
treat disease might one day be preventable.Alzheimer’s is the most common form of
dementia, there being roughly 90,000 patients with the disease in Sweden today. The
underlying causes of Alzheimer’s disease are still something of a mystery, but there
are a number of known risk factors. The most common is a variant of a certain gene that
governs the production of apolipoprotein E, one of the functions of which is to transport
cholesterol. The gene variant is called apoE4 and is found in 15-20 per cent of the
population.For her doctoral thesis, Susanne Akterin studied mice that had been genetically
modified to mimic the effects of apoE4 in humans. The mice were then fed for nine months
on a diet rich in fat, sugar and cholesterol, representing the nutritional content of most
fast food.“On examining the brains of these mice, we found a chemical change not
unlike that found in the Alzheimer brain,” says Ms Akterin, postgraduate at KI
Alzheimer’s Disease Research Center.
In a study published in the Journal of Alzheimer's Disease, researchers from the
University of Aberdeen report that the drug memantine, used for the treatment of
Alzheimer's disease and praised as "the first and only representative of a new class
of Alzheimer drugs" works in fact similar to other existing compounds, and is
beneficial only in a narrow concentration range. They further indicate that the complex
pharmacological profile of memantine requires careful consideration concerning suitable
doses and suitable patient groups.
Mutant proteins result in
infectious prion disease in mice
A worldwide group of scientists, including Christina J. Sigurdson, D.V.M., Ph.D.,
assistant professor of pathology at the UCSD School of Medicine, has created an infectious
prion disease in a mouse model, in a step that may help unravel the mystery of this
progressive disease that affects the nervous system in humans and animals. The study, led
by Professor Dr. Adriano Aguzzi of the Institute of Neuropathology at the University of
Zurich in Switzerland, was designed to investigate the specific changes in the prion
protein that may contribute to chronic wasting disease (CWD). CWD is a highly infectious
prion disease found in free-ranging deer and elk that is similar to bovine spongiform
encephalopathy (BSE, or "mad cow disease") in cattle and Creutzfeldt-Jakob
disease in humans. Prion diseases are thought to be a result of a misfolded form of the
prion protein that induces formation of amyloid plaques in the brain – changes that
are also seen in patients with Alzheimer's disease.
Treating Sleep Apnea in
Alzheimer’s Patients Helps Cognition
Continuous positive airway pressure (CPAP) treatment seems to improve cognitive
functioning in patients with Alzheimer’s disease who also suffer from obstructive
sleep apnea, according to the results of a randomized clinical trial conducted at the
University of California, San Diego. The study – led by Sonia Ancoli-Israel, Ph.D.,
professor of psychiatry at the UC San Diego School of Medicine and one of the
nation’s preeminent experts in the field of sleep disorders and sleep research in
aging populations – was published in the November issue of the Journal of the
American Geriatrics Society.
New study identifies link between
Alzheimer's disease biomarkers in healthy adults
A study published in the November issue of the Journal of Alzheimer's Disease provides an
insight into normal, physiological levels and association between proteins involved in
development of Alzheimer's disease. A group of scientists and physicians from the
University of Washington and Puget Sound Veterans' Affairs Health Care System in Seattle,
in collaboration with groups from the University of Pennsylvania and the University of
California San Diego, performed a study in cognitively normal and generally healthy
adults, from young to old (age range 21-88 years), of both genders, measuring levels of
different brain-derived molecules associated with Alzheimer's disease. Investigators
determined that cerebrospinal fluid (CSF) levels of apolipoprotein E (apoE), one of the
most important proteins involved in transfer of fatty substances between different brain
cells, are highly correlated with the levels of proteins known to be involved in
development of Alzheimer's disease, amyloid precursor protein (APP) and tau. While many
studies have previously shown that apoE gene is very important for Alzheimer's disease
development, the connection between apoE protein and other relevant CSF markers in healthy
adults was not known. Although this type of study cannot establish causal associations,
the results strongly suggest that the CSF levels of apoE may explain a significant
proportion of the levels of APP- and tau-related biological markers in the healthy human
brain, indicating a strong physiological link between apoE, APP and tau. In other words,
the study points to a possibility that modulation of the levels of apoE may affect the
levels of APP and tau in the brain.
New method developed to identify
genetic determinants of Alzheimer's disease
A rapid and accurate DHPLC assay for determination of apolipoprotein E genotypes has been
developed by researchers from the Department of Medical Genetics, School of Basic Medical
Sciences, Southern Medical University, Guangzhou, China. This assay combines PCR and DHPLC
and can be used to conduct efficient genotyping of the human population, which in turn
will help in the diagnosis and treatment of Alzheimer’s disease. A description of the
assay has been published this month in the Journal of Alzheimer's Disease.
