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 seed polyphenolic 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. Pasinetti can be reached at [email protected].