A gene that's been known for two decades as the largest inheritable risk for developing Alzheimer's disease mostly affects the brains of women, not men, according to a team of researchers from Stanford and the University of California at San Francisco.

The gene variant known as APOE4 is the most common genetic risk factor for Alzheimer's only about 15 percent of people carry the gene, but it's found in more than half of all Alzheimer's patients.

The variant was first connected to Alzheimer's in 1993, but doctors and scientists for the most part have been unaware of any gender differences, despite early studies that showed an increased risk for women with the gene.

The new research, which is being published Wednesday in the Journal of Neuroscience, looked at two biological indicators or biomarkers associated with Alzheimer's disease: decreased activity in a brain network related to memory and increased levels of the tau protein in spinal fluid. Women with the APOE4 gene were more likely to test positive for both markers than men who had the gene and women who didn't have the gene.

The findings will not have an immediate clinical impact few people are encouraged to learn their APOE4 status because there is no treatment for Alzheimer's. But the results could open new research possibilities, such as the relationship between hormones and Alzheimer's or other gender differences that could make women with the gene more vulnerable, scientists said.

"We haven't been able to get much insight into how APOE is affecting increased risk. This might be a big clue," said Dr. Michael Greicius, medical director of the Stanford Center for Memory Disorders and senior author of the study.

The older study of the APOE4 gene found that women with one copy of the gene were four times more likely than anyone without the gene to develop Alzheimer's; men with a single copy had no increased risk. Both men and women, however, were as much as 14 times more likely to develop Alzheimer's if they had two copies of the gene. But that's a rare combination only 2 percent of the population has two copies.

The APOE4 gene, along with other genetic risk factors, has become increasingly important in research for treating the disease. Genetic research can help scientists better understand what causes Alzheimer's and it may lead to treatments that target specific biological mechanisms of the disease.

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Alzheimer's risk gene mostly affects women

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