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 Maria 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
abnormally high molecular weight soluble oligomerized amyloid peptides
highly implicated in mechanism associated with deterioration of cognitive
functions and eventually dementia in Alzheimer?s disease.

The researchers tested a grape seedpolyphenolic extract product sold as
MegaNatural-AZ, made by Polyphenolics, which in part supported the study
conducted at Mount Sinai School of Medicine together with the National
Center for Complementary and Alternative Medicine (NCCAM). Polyphenolic
compounds are naturally compounds 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 analogous to Alzheimer?s disease. They
exposed pre-symptomatic ?Alzheimer?s mice? to it or placebo daily for five
months. The daily dose of the grape seed polyphenolic extract was equivalent
to the average amount of polyphenolics consumed by a person on a daily
basis.

After the five-month period, Alzheimer?s mice were at an age where they
normally develop signs of disease. However, the extract exposure reduced
high molecular oligomerized amyloid beta accumulation and eventual amyloid
plaque formation in brains of Alzheimer?s mice, and it also reduced
cognitive decline: compared to placebo, extract-exposed Alzheimer?s mice
showed improved spatial memory. These data suggest that before symptoms
begin, the grape seed extract may prevent or postpone plaque formation and
slow cognitive deterioration associated with Alzheimer?s disease.

Moderate consumption of red wine - approximately one glass for women and two
glasses for men, according to the Food and Drug Administration - and its
constituent grape compounds has reported health benefits, particularly to
cardiovascular function. Pasinetti previously found that red wine reduced
cognitive decline in mice genetically modified to develop Alzheimer?s
disease. In subsequent studies, Pasinetti and colleagues have attempted to
isolate which of the nearly 5,000 molecules contained in red wine are
important in disease prevention. ?Our intent is to develop a highly
tolerable, nontoxic, orally available treatment for the prevention and
treatment of Alzeheimer?s dementia,? Pasinetti said.

?The potential of natural compounds to provide real health benefits to brain
function is only now beginning to be realized by brain researchers. The
lesson they may eventually learn is that sometimes you just can?t improve
upon Mother nature,? said Gary Arendash, PhD, of The Byrd Alzheimer?s
Institute, an expert unaffiliated with the study.

Chemical analysis showed that the major polyphenol components in the study?s
grape seed extract product are catechin and epicatechin, which are also
abundant in tea and cocoa. These components differ from resveratrol, a
polyphenol that has been reported to reduce amyloid beta secretion in cells
and generally increase lifespan by mimicking calorie restriction.
Resveratrol appears to be effective only at extremely high doses, which may
limit its use in people. In contrast, the catechins in the extract product
studied appear to be effective at much lower doses.

Karen Hsiao Ashe, MD, PhD, at the University of Minnesota, another expert
unaffiliated with the study, cautioned that additional research must be
completed before these findings translate to a human population. ?Unanswered
questions pertaining to the polyphenolic extract?s use in humans to prevent
Alzheimer's disease include: when to start taking it, for how long, how much
to take, and most importantly, how does a person know if it is helping to
prevent the oligomerization of amyloid beta protein in the brain? These
questions must be answered before grape seeds polyphenolics can be
recommended as a preventive measure for Alzheimer's disease,? Ashe said.
Clinical studies testing the beneficial role of MegaNatural-AZ in Alzheimer?s
disease dementia are currently in progress.

The research was performed at the Center of Excellence for Research in
Complementary and Alternative Medicine in Alzheimer?s Disease directed by
Dr. Pasinetti at Mount Sinai School of Medicine and was supported the
National Center for Complementary and Alternative Medicine at the National
Institutes of Health NIH and in part by Polyphenolics, the maker of
MegaNatural AZ (the extract studied) and by the U. S. Department of Veterans
Affairs, Japan Human Science Foundation, and the Alzheimer?s Association.

The Journal of Neuroscience is published by the Society for Neuroscience, an
organization of more than 38,000 basic scientists and clinicians who study
the brain and nervous system.
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