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Two proteins may help prevent Alzheimer's brain plaques

St. Louis, Jan. 21, 2004 -- A study led by researchers at Washington University School of Medicine in St. Louis suggests two proteins work together in mice to prevent formation of brain plaques characteristic of Alzheimer's disease.

The proteins, apolipoprotein E (apoE) and clusterin, appear to act as "chaperones" orchestrating the clearance of potentially hazardous molecules out of the brain. Ironically, these proteins also have been implicated in a key stage of plaque formation. The study appears in the Jan. 22 issue of the journal Neuron.

"This is one of the first demonstrations in living animals that these proteins affect amyloid clearance," says David H. Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "Our findings suggest it is worthwhile to explore the use of drugs or therapies to alter or perhaps increase the expression of these proteins as a potential treatment for Alzheimer's disease."

Holtzman, who also is the Charlotte and Paul Hagemann Professor of Neurology and professor of molecular biology and pharmacology, led the study; Ronald DeMattos, Ph.D., formerly an instructor in neurology, and John R. Cirrito, a graduate student in neuroscience, are co-first authors. The team collaborated with Eli Lilly and Company, where DeMattos now works.

A key step in the development of Alzheimer's disease is the formation of brain plaques. Studies suggest these plaques form when the protein amyloid beta (Abeta) is converted from its soluble to its insoluble form and coalesces into hair-shaped threads called fibrils. Unable to dissolve or be cleared out of the brain, the fibrils eventually clump together and become the amyloid plaques that are a hallmark of Alzheimer's.

In previous studies, Holtzman's team was instrumental in showing both apoE and clusterin promote the formation of these fibrils. Their new paper confirms that in mice genetically engineered to develop Alzheime
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Contact: Gila Z. Reckess
reckessg@wustl.edu
314-286-0109
Washington University School of Medicine
21-Jan-2004


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