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February 24, 2004

Early Vitamin E Supplements Stem Development of
Hallmark Alzheimer’s Symptoms in Mice

(Philadelphia, PA) - Vitamin E, a well-known antioxidant, has been used to treat Alzheimer’s disease, but with mixed results, especially in patients with advanced symptoms. A risk factor for Alzheimer’s is oxidative stress, a clinical condition characterized by an excessive production of reactive chemicals in the brain, which can damage important regions of this organ.

Domenico Praticò, M.D., assistant professor of pharmacology at the University of Pennsylvania School of Medicine, and colleagues tested the idea that timing of vitamin E supplementation for treating Alzheimer’s might be an important factor in its effectiveness. They found that vitamin E given to young transgenic mice before the formation of telltale plaques reduces by up to half the levels of amyloid deposited in the brain over time compared to aged mice on the same regimen. This study appears in the February edition of The FASEB Journal.

“Our findings indicate that an antioxidant is important to cure or prevent disease only if given at a very early stage,” says Praticò. “If given when the disease is already established the chances of a positive effect are very small.”

The researchers used a well-characterized transgenic mouse that expresses a mutant gene present in humans and forms Alzheimer’s plaques (similar to the ones found in humans) in the brain starting at about 11 to 12 months. One group of mice received vitamin E at five months, before plaques start to form. Another group started at 14 months--a time when much plaque had already been deposited--with the same amount of vitamin E. They followed each group for eight months and compared their outcome with controls that did not receive vitamin E. The young group showed a 50 percent reduction in the number of plaques deposited in brain tissue as compared to the older mice. “This group didn’t show any significant difference in plaque reduction as compared to controls, suggesting that once the plaque is deposited there’s very little that an antioxidant can do,” says Praticò. This finding also indicates that other mechanisms may play a role in the disease once established.

The immediate implications of these findings are simple, especially for patients diagnosed with mild cognitive impairment (MCI), a possible precursor to Alzheimer’s: Start taking vitamin E early. “They will benefit the most,” says Praticò. “ Considering that up to 50 percent of patients with MCI will develop Alzheimer’s within four years, and the fact that recent epidemiological studies have clearly shown that intake of antioxidants, in particular vitamin E, lowers the risk of Alzheimer’s, MCI patients will be the most appropriate target for this therapy.”

Penn scientists also contributing to this research are Syuan Sung, Yuemang Yao, Kunihiro Uryu, Hengxuan Yang, Virginia M-Y Lee, and John Q. Trojanowski. This study was funded by the National Institutes of Health, The Alzheimer Association, and the American Heart Association.

Dr. Pratico, can be contacted at domenico@spirit.gcrc.upenn.edu or 215-898-6446.

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Release available online at http://www.uphs.upenn.edu/news/News_Releases/feb04/vitamineE.htm