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Researchers Look to Red-Wine Compounds for Alzheimer's Cure

Polyphenols, including resveratrol, can control proteins that build up in brain cells and inflict damage; more research needed

Jacob Gaffney
Posted: December 15, 2008

Two teams of researchers from opposite sides of the country say they may have figured out how compounds found in red wine combat the onset of Alzheimer's disease. Now they are focusing their efforts into developing a possible treatment or cure.

Scientists at UCLA, in collaboration with a team at Mt. Sinai School of Medicine in New York, recently announced their findings that grape seed-derived polyphenols block and neutralize the toxic plaques that build up in the brains of Alzheimer's patients and kill brain cells. Two proteins known as amyloid-beta peptides are associated with Alzheimer's. These long protein strands tend to clump together, forming plaques that kill surrounding brain cells. The UCLA and Mt. Sinai researchers found that the grape polyphenols blocked the formation of the plaques. They also found that the polyphenols decreased the toxicity of the plaques when the compounds were bonded with amyloid-beta peptides before being added to brain cells.

"If the amyloid-beta proteins can't assemble, toxic aggregates can't form, and thus there is no toxicity," said co-author David Teplow, a UCLA neurology professor, in a statement. "Our work in the laboratory, and Mt. Sinai's Dr. Giulio Pasinetti's work in mice, suggest that administration of the compound to Alzheimer's patients might block the development of these toxic aggregates, prevent disease development and also ameliorate existing disease." Earlier research by Pasinetti also found that Cabernet Sauvignon reduces the levels of amyloid-beta peptides in mice's brains.

The results were published in the Nov. 21 issue of the Journal of Biochemistry. Teplow also said that questions remain about whether the best potential treatment will be natural polyphenols or a synthesized lab version. "The answer depends on the therapeutic dose determined in clinical trials and whether dietary introduction of the polyphenols will produce these levels in the brain," he said. "It may be possible, for example, to create a pill that concentrates the appropriate polyphenols and thereby produces therapeutic doses in the brain."

The UCLA team isn't the only one making progress in the fight against Alzheimer's. In mid-November, speaking at the Society for Neuroscience's annual meeting in Washington, D.C., researcher Valorie Vingtdeux, of the Manhasset, N.Y., based Feinstein Institute for Medical Research, offered an alternative theory for how red-wine compounds may help in the fight against Alzheimer's. Vingtdeux and her team have found that the red wine compound resveratrol appears to activate a specific enzyme that controls amyloid-beta peptide levels.

The enzyme is called AMPK. When levels of adenosine triphosphate (ATP), the molecule used by cells as an energy source, drop, AMPK is activated. The enzyme prepares the body's cells for the metabolic change. Vingtdeux observed that it also lowers amyloid-beta levels. In her research, overseen by noted Alzheimer's researcher Philippe Marambaud, she found that resveratrol also activates AMPK, which then lowers the amount of the dangerous amyloid-beta peptides in the brain.

Feinstein Institute scientists are now screening a litany of chemicals to see whether there are any compounds that could mimic the effects of resveratrol. The amounts found in grapes and wine are too small to have a benefit, so Vingtdeux's team is looking to develop a synthetic version. Furthermore, the scientists are still unclear on how resveratrol activates AMPK.

Both the UCLA and Mt. Sinai teams and the Feinstein Institute are exploring clinical trials with humans. Much more research remains to be done. "Resveratrol in grapes may never reach the concentrations required," said Marambaud. "However, grapes and wine contain more than 600 different such components. We cannot exclude the possibility that several compounds work in synergy with small amounts of resveratrol to slow down the progression of the neurodegenerative process in humans."

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