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Benefits from Alzheimer's plaque-producing reaction? Science study proposes role in gene expression

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The molecule that spawns "plaque" buildup in the brains of Alzheimer's patients may also play a role in normal gene expression, suggests a study using cultured cells. The study will be published in the 6 July issue of the international journal, Science.

If these findings prove true in humans, they may help scientists understand why the plaques form and perhaps even the basic mechanisms that lead to the disease.

The study also raises the possibility of unwanted side effects from drugs intended to prevent plaque formation, by revealing a biological use for the reaction that produces the plaque molecules. Such drugs are currently under investigation as possible Alzheimer's therapies.

Researchers have long wondered about the normal function of the parent protein to the plaque molecules--the "amyloid precursor protein," or "APP," which is embedded in the cell membranes of neurons in the brain.

The protein is split into pieces by a series of enzymes. The last of these reactions, called "gamma cleavage," cuts the remaining molecule into two smaller pieces.

The infamous Alzheimer's plaques form from one of these pieces, the "beta-amyloid" peptide, which is secreted from the cell. The other piece is the APP "tail," which dangles from the membrane into the cell. Its function has thus far been a mystery.

In their Science study, authors Xinwei Cao and Thomas C. Sdhof of the University of Texas Southwestern Medical Center and Howard Hughes Medical Institute propo
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Contact: Ginger Pinholster
gpinhols@aaas.org
202-326-6421
American Association for the Advancement of Science
5-Jul-2001


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