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Brain damage found in cognitively normal people with Alzheimer's marker
Date:3/10/2009

tic hallmark of the disease. In an earlier study, the same Washington University researchers showed that when A-beta 42 decreases in CSF, it begins to build up in the brain.

"The new results show that something associated with amyloid deposition in the brain − either the amyloid itself or some toxic product of it − is causing brain damage in people who are still cognitively normal," says Holtzman.

For the study, led by Anne Fagan, Ph.D., research associate professor of neurology, scientists analyzed CSF samples and brain scans of two groups of subjects at the university's Alzheimer's Disease Research Center. The first group of 29 volunteers had very mild cognitive impairment; the remaining 69 volunteers were cognitively normal. Their ages ranged from 60 to 91.

Researchers analyzed CSF samples and took magnetic resonance imaging (MRI) scans of subjects' brains. They used a computer program to analyze the MRI scans and determine whole brain volume, a measurement of the amount of space taken up by a patient's gray and white matter minus the CSF fluid circulating in the skull.

Participants with normal levels of A-beta 42 in their CSF had whole brain volumes within expected ranges. But in both the cognitively impaired subjects and in cognitively normal volunteers with decreased CSF A-beta 42, the size of the brain was smaller.

In addition to A-beta 42, researchers analyzed CSF levels of a family of proteins called tau proteins. These proteins are a component of structures called neurofibrillary tangles that increase as Alzheimer's disease progresses. Scientists believe increased levels of tangles in the brain lead to increased CSF tau levels.

Researchers found CSF tau levels did not increase until subjects became mentally impaired.

"We've thought for some time that in Alzheimer's disease, amyloid builds up first followed by an increase in tangle accumulation," Holtzman says. "This is some of the f
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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

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