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January 4, 2011

Wine Therapy

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  Alzheimer's Disease Fact Sheet

Nutrition and Alzheimer's Disease

Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University

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Making a toast to your health could have new meaning this holiday season. Researchers have identified a substance in red wine that may help prevent Alzheimer's disease. This ScienCentral News video explains.

Red or White?

When your host offers you red or white wine at her annual holiday party this year, there may be a good reason to choose red. In a series of laboratory tests, researchers in New York found new evidence that an antioxidant found in red wine, called resveratrol, helps clear away the basic building blocks of Alzheimer plaques.

The finding, published in the Journal of Biological Chemistry, contributes to the growing body of research that suggests moderate red wine consumption may help prevent a number of diseases, including age-related dementias, heart disease, and cancer. The researchers, led by neurobiologists Philippe Marambaud and Peter Davies, say their study also identifies a previously unknown chemical pathway that may one day be tapped to design new drugs to fight Alzheimer's disease.

"This is potentially a protective [compound], a compound that we could give you at age 40 or 50, whatever age you'd like to start, to protect against the development of Alzheimer's disease," says professor Davies from the Albert Einstein College of Medicine, who was the senior author on the paper.

The researchers tested several different antioxidants on cells filled with amyloid peptides.

In the brains of Alzheimer's patients, amyloid peptides bind together into plaques that lodge themselves between brain cells. The amyloid peptides and the plaques have a toxic effect on brain cells that cause them to die. But it's difficult to grow these plaques between cells in laboratory dishes, so the researchers grew the plaque's building blocks - the amyloid peptides - inside cells. Subsequently, they mixed the cells with a variety of antioxidants. They wanted to see if any of the antioxidants would reduce the number of amyloid peptides in the cells.

Amyloid plaques form in the brains of Alzheimer's sufferers.
image: National Institute on Aging
"We observed that only resveratrol was very potent, very active in doing so," says the study's lead author Marambaud of the Litwin-Zucker Research Center for the Study of Alzheimer's Disease and Memory Disorders.

The researchers stress that resveratrol does not prevent amyloid peptides from forming, but just helps reduce their numbers once they are in place. Resveratrol works by triggering a naturally occurring "protein-eating" complex, called a proteasome. The proteasome ultimately disposes of the amyloid peptides.

"Resveratrol seems to activate a [chemical] pathway that is there normally… this pathway is something the body has, but isn't using to it's full capacity, at least in the absence of resveratrol," Davies says.

This pathway is really a "novel finding," says Li Gan, a specialist in the molecular mechanisms of Alzheimer's disease at the Gladstone Institute and at the University of California, San Francisco, who also recently reported a separate mechanism in the Journal of Biological Chemistry by which resveratrol also reduces the toxic effect of amyloid peptides on brain cells.

She says further research is needed to confirm both her study and the one done by the New York team, but if both show resveratrol to work in additional cell cultures and in animal studies, then it could be that resveratrol helps to both reduce the number of amyloid peptides as well as their toxic effect on brain cells.

"The two beneficial effects of resveratrol is like killing two birds with one stone," she says.

New Drugs

While the researchers hope they can target this chemical pathway in cells and use resveratrol as a model for future Alzheimer's drugs, Marambaud says it will not be an easy task. "It's unlikely that resveratrol will work in animals or even in humans because… the kidney system will get rid of resveratrol very quickly and there is no chance it will reach the brain," he explains.

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Marambaud and Davies' team plans to try and get around this problem by making a much more potent version of resveratrol. They are also continuing their research to see if resveratrol helps to degrade Alzheimer's tangles, the other microscopic protein typically found in the brains of Alzheimer's patients.

In the meantime, Marambaud warns that drinking red wine for your health, is only healthful in moderation.

This research appeared in the Journal of Biological Chemistry in November, 2005 (280: 28912-28916). The research performed by Philippe Marambaud and Peter Davies was funded by the National Institutes of Mental Health and the American Health Assistance Foundation.

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