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Alzheimer's gene affects women, not men: study

WASHINGTON -- A gene variant that presents the most common inherited risk factor for Alzheimer's disease has been shown for the first time to affect older women but not men, according to a U.S. study Tuesday.

The findings suggest a possible reason why Alzheimer's is more common in women than in men, and implies that men who test positive for a single copy of the ApoE4 gene should not be considered at higher risk for the disease.

Among healthy older women with the gene variant, ApoE4, researchers observed changes in brain activity and higher levels of a protein called tau in their cerebrospinal fluid, both telltale changes linked to Alzheimer's.

However, these signals were not found in healthy older men with the same gene variant, said the study by Stanford University scientists in the June 13 edition of the Journal of Neuroscience.

The research was based on functional MRI scans of 131 healthy people, with a median age of 70.

Researchers found that healthy older women with at least one ApoE4 allele showed a loss of synchronization in the brain's memory network. The phenomenon was not observed among men.

A second part of the study was based on a public database maintained by the Alzheimer's Disease Neuroimaging Initiative, in which healthy 55 to 90-year-old volunteers agree to have their cerebrospinal fluid analyzed for research.

Researchers examined the records of 91 people, divided them by gender and again by ApoE4 status, and found that ApoE4 women, not ApoE4 men, showed fluid that was “substantially enriched in tau.”

“It was only possible to see these differences in tau levels when we separated the patients by gender,” said Michael Greicius, senior author of the study and medical director of the Stanford Center for Memory Disorders.

The findings might offer a clue to why more women suffer from the degenerative disorder than men, he added, noting that for every three women with the disease, only about two men have it.

“This disparate impact of ApoE4 status on women versus men might account for a big part of the skewed gender ratio,” he said.

The study included only people whose “ability to think and remember appeared normal for their age,” the study noted, meaning that the brain changes that the study picked up were found before the onset of memory loss and disorientation.

Co-authors on the study came from the University of California-San Francisco and Los Angeles (UCLA).

According to the National Institute on Aging, the apolipoprotein E (APOE) gene is found on chromosome 19 and “contains the instructions for making a protein that helps carry cholesterol and other types of fat in the bloodstream.”

The ApoE4 variant is present in about 25-30 percent of the population, and in about 40 percent of all people with late-onset Alzheimer's, it said.

There is no cure for Alzheimer's, which affects about five million people in the United States and nearly 30 million worldwide.

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