Alzheimer's risk gene

Alzheimer's risk gene disrupts brain function in healthy older women, but not men

June 12, 2012 in Alzheimer's disease & dementia

A team led by investigators at the Stanford University School of Medicine has found that the most common genetic risk factor for Alzheimer's disease disrupts brain function in healthy older women but has little impact on brain function in healthy, older men. Women harboring the gene variant, known to be a potent risk factor for Alzheimer's disease, show brain changes characteristic of the neurodegenerative disorder that can be observed before any outward symptoms manifest.

Both men and women who inherit two copies (one from each parent) of thisgene variant, known as ApoE4, are at extremely high risk for Alzheimer's. But the double-barreled ApoE4 combination is uncommon, affecting only about 2 percent of the population, whereas about 15 percent of people carry a single copy of this version of the gene.

The Stanford researchers demonstrated for the first time the existence of a gender distinction among outwardly healthy older people who carry the ApoE4 variant. In this group, women but not men exhibit two telltale characteristics that have been linked to Alzheimer's disease: a signature change in their brain activity, and elevated levels of a protein called tau in their cerebrospinal fluid.

One implication of the study, which will be published June 13 in the Journal of Neuroscience, is that men revealed by genetic tests to carry a single copy of ApoE4 shouldn't be assumed to be at elevated risk for Alzheimer's, a syndrome afflicting about 5 million people in the United States and nearly 30 million worldwide. The new findings also may help explain why more women than men develop this disease, said Michael Greicius, MD, assistant professor of neurology and neurological sciences and medical director of the Stanford Center for Memory Disorders. Most critically, identifying the prominent interaction between ApoE4 and gender opens a host of new experimental avenues that will allow Greicius' team and the field generally to better understand how ApoE4 increases risk for Alzheimer's disease./.../