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Alzheimer's risk gene disrupts brain's wiring 50 years before disease hits
Date:5/13/2011

What if you were told you carried a gene that increases your risk for Alzheimer's disease? And what if you were told this gene starts to do its damage not when you're old but when you're young?

Brace yourself.

Scientists know there is a strong genetic component to the development of late-onset Alzheimer's. In 1993, researchers discovered a gene known as ApoE4 carried by about a quarter of us that triples the risk for getting Alzheimer's. In 2009, three more risky genes were discovered, and one of them, called clusterin, or CLU, was found to up the risk of getting Alzheimer's by another 16 percent.

But nobody could explain what the CLU gene actually did. Now, UCLA researchers know, and the explanation is a doozy: This risk gene begins to damage your brain a full 50 years before people normally get Alzheimer's.

In the current online edition of the Journal of Neuroscience, Paul Thompson, a UCLA professor of neurology, and his colleagues report that the C-allele of the CLU gene (an allele is one of two or more forms of a gene), which is possessed by 88 percent of Caucasians, impairs the development of myelin, the protective covering around the neuron's axons in the brain, making it weaker and more vulnerable to the onset of Alzheimer's much later in life.

The researchers scanned the brains of 398 healthy adults ranging in age from 20 to 30 using a high-magnetic-field diffusion scan (called a 4-Tesla DTI), a newer type of MRI that maps the brain's connections. They compared those carrying a C-allele variant of the CLU gene with those who had a different variant, the CLU T-allele.

They found that the CLU-C carriers had what brain-imaging researchers call lower "fractional anisotropy" a widely accepted measure of white-matter integrity in multiple brain regions, including several known to degenerate in Alzheimer's. In other words, young, healthy carriers of the CLU-C gene risk variant showed a
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Contact: Mark Wheeler
mwheeler@mednet.ucla.edu
310-794-2265
University of California - Los Angeles
Source:Eurekalert

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