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Families shed light on likely causative gene for Alzheimer's
Date:5/14/2008

The genetic profile of two large Georgia families with high rates of late-onset Alzheimer's disease points to a gene that may cause the disease, researchers say.

Genetic variations called single nucleotide polymorphisms, or SNPs, are common in DNA, but this pattern of SNPs shows up in nine out of 10 affected family members, says Dr. Shirley E. Poduslo, neuroscientist in the Medical College of Georgia Schools of Medicine and Graduate Studies and the Charlie Norwood Veterans Affairs Medical Center in Augusta.

The 10th family member had half the distinctive pattern. The SNPs also were found in the DNA of 36 percent of 200 other late-onset patients stored in the Alzheimers' DNA Bank.

"We were shocked; we had never seen anything like this before," Dr. Poduslo says of findings published online in the American Journal of Medical Genetics. "If we looked at unaffected spouses, their SNPs were all different. The variants consistently found in affected siblings are suggesting there is something in this gene. Now we have to go back and find what is in this gene that is making it so unique for Alzheimer's patients."

The variation was in the TRPC4AP gene, part of a large family of genes that is not well-studied but is believed to regulate calcium. Calcium is needed throughout the body but its dysregulation can result in inflammation, nerve cell death and possibly plaque formation as well, she says.

The finding provides new directions for research and possibly new treatment targets, Dr. Poduslo says. It also shows the important role large families affected by a disease can have in determining the cause of the disease.

The specific genetic mutation responsible still must be identified and will require sequencing the very large gene, or determining the order of the base pairs that form the rungs of the ladder-like DNA, Dr. Poduslo says. An SNP represents a change in either side of a rung. "The mutation could be a deletion
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

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