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International TGen-led team finds link between brain protein and Alzheimer's disease
Date:9/15/2008

e centers, including three European organizations representing German, Dutch and Norwegian populations.

Gene expression study

The gene expression study examined tissues from six regions of the brain among 47 deceased individuals. The brain tissue samples were provided by three Alzheimer's disease centers: Washington University in St. Louis, Mo.; Duke University in Durham, N.C.; and Sun Health Research Institute in Sun City, Ariz.

KIBRA, and a subset of other molecules directly interacting with it, were significantly altered in regions of the brain involved in Alzheimer's disease pathology. The regions investigated included the hippocampus, entorhinal cortex, posterior cingulate cortex, middle temporal gyrus, and superior frontal gyrus. However, they were not altered in a region of the brain typically unaffected by the disease -- the primary visual cortex.

Positron Emission Tomography scans

PET scans of 67 non-carriers of the KIBRA T-allele, and 69 carriers -- all with close relatives diagnosed with Alzheimer's -- showed that non-carriers exhibited, on average, similar alterations in the metabolic activity of key brain regions known to be altered in the earliest stages of the disease. All 136 individuals were mentally-normal, late-middle-aged Phoenix-area volunteers solicited from newspaper advertisements. They ranged in age from 47 to 68, with an average age of 55.

Scans showed that individuals without the KIBRA T-allele -- those with only KIBRA C-alleles from their mother and from their father -- had less metabolic brain activity when compared to those individuals carrying the T-allele -- from either their mother or father, or both. These differences were found in the precuneus and posterior cingulated regions of the brain affected in the earliest stages of Alzheimer's.

Previous work led by Reiman illustrated a similar finding when individuals were grouped according to whether they carried the mo
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Contact: Steve Yozwiak
syozwiak@tgen.org
602-343-8704
The Translational Genomics Research Institute
Source:Eurekalert

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