Gene Variant May Hike Women's Risk of Alzheimer's

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By Amanda Gardner
HealthDay Reporter
Monday, January 12, 2009; 12:00 AM

MONDAY, Jan. 12 (HealthDay News) -- Scientists have discovered a gene variant on the X chromosome that appears to increase the risk of developing Alzheimer's disease.

The risk was most pronounced in women with the variant on both X chromosomes, although both women and men with just one variant of the gene were also at greater risk.

"What you have in a nutshell is the first study showing a gene on the X chromosome and the first sex-specific effect [for Alzheimer's]," said Dr. Steven Younkin, senior author of the paper published online Jan. 11 in the journal Nature Genetics. "It does not mean women are at increased risk for Alzheimer's."

Although the presence of the mutation offers strong evidence of a heightened risk, further research needs to be done to determine how big of a risk, added Younkin, who is the George M. Eisenberg professor of neuroscience at the Mayo Clinic College of Medicine in Jacksonville, Fla.

Dr. Anton Porsteinsson, director of the Alzheimer's Disease Care, Research and Education Program and the Memory Disorders Clinic at the University of Rochester School of Medicine, called the finding intriguing.

"To me, the fact that it's X-linked is intriguing because of the fact that there are more women than men with Alzheimer's disease," he said.

According to background information in the paper, late-onset Alzheimer's disease is the most common cause of dementia in older people, affecting about 10 percent of those aged 65 or over.

A mutation in the APOE 4 gene is the only genetic risk factor that has been "solidly" linked to the risk of late-onset Alzheimer's, Porsteinsson said. Other genes have been linked to early onset disease.

"The effort to find additional genetic variants has been difficult," Younkin said.

For the study, Younkin and his colleagues scanned hundreds of thousands of genes in 844 people with Alzheimer's disease and 1,255 healthy people who served as "controls."

There was nothing genetic in the first pass that the researchers could say unequivocally was associated with Alzheimer's disease.

But a second pass, this one on even more patients and controls, uncovered a strong association between a mutation on the PCDH11X gene and Alzheimer's disease.

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