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Scientists identify 'missing link' in process leading to Alzheimer's disease

Scientists at the University of Virginia have identified what appears to be a major missing link in the process that destroys nerve cells in Alzheimer's disease, an incurable disease that slowly destroys memory and cognitive abilities. The findings are reported in the Nov. 20, 2006, issue of the Journal of Cell Biology (http://www.jcb.org/cgi/content/full/175/4/541) and could eventually lead to new drugs that target and disrupt specific proteins that conspire in the brain to cause Alzheimer's.

In Alzheimer's disease, two kinds of abnormal structures accumulate in the brain: amyloid plaques and neurofibrillary tangles. The plaques contain fibrils that are made from protein fragments called "beta-amyloid peptides." The tangles also are fibrous, but they are made from a different substance, a protein called "tau." In the new U.Va. study, the researchers found a deadly connection between beta-amyloid and tau, one that occurs before they form plaques and tangles, respectively.

According to George Bloom, the senior author of the study and a professor of biology and cell biology at U.Va., this connection causes the swiftest, most sensitive and most dramatic toxic effect of beta-amyloid found so far. What makes it most remarkable, though, is that it requires a form of amyloid that represents the building blocks of plaques, so called "pre-fibrillar beta-amyloid," and it only happens in cells that contain tau. Even though they account for just ~10 percent of the cells in the brain, nerve cells are the major source of tau, which likely explains why they are specifically attacked in Alzheimer's disease.

The researchers used cultured mammalian cells that either did or did not make tau to study how cells respond to beta-amyloid. They found that pre-fibrillar, but not fibrillar beta-amyloid works together with tau to break apart microtubules highways along which "synapse" replacement parts move rapidl
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Contact: George Bloom
gsb4g@virginia.edu
434-243-3543
University of Virginia
7-Feb-2007


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