Gene variant puts women at higher risk of Alzheimer's than it does men, study finds

PUBLIC RELEASE DATE:

14-Apr-2014

Contact: Bruce Goldman goldmanb@stanford.edu 650-725-2106 Stanford University Medical Center

STANFORD, Calif. Carrying a copy of a gene variant called ApoE4 confers a substantially greater risk for Alzheimer's disease on women than it does on men, according to a new study by researchers at the Stanford University School of Medicine.

The scientists arrived at their findings by analyzing data on large numbers of older individuals who were tracked over time and noting whether they had progressed from good health to mild cognitive impairment from which most move on to develop Alzheimer's disease within a few years or to Alzheimer's disease itself.

The discovery holds implications for genetic counselors, clinicians and individual patients, as well as for clinical-trial designers. It could also help shed light on the underlying causes of Alzheimer's disease, a progressive neurological syndrome that robs its victims of their memory and ability to reason. Its incidence increases exponentially after age 65. An estimated one in every eight people past that age in the United States has Alzheimer's. Experts project that by mid-century, the number of Americans with Alzheimer's will more than double from the current estimate of 5-6 million.

According to the Alzheimer's Association, it is already the nation's most expensive disease, costing more than $200 million annually. (The epidemiology of mild cognitive impairment is fuzzier, but this gateway syndrome is clearly more widespread than Alzheimer's.)

The number of women with Alzheimer's far exceeds that of men with the condition. That's partly because women on average live longer than men. But greater longevity explains only part of women's increased susceptibility to Alzheimer's. "Even after correcting for age, women appear to be at greater risk," said Michael Greicius, MD, assistant professor of neurology and neurological sciences and medical director of the Stanford Center for Memory Disorders.

Greicius was the senior author of a study, to be published April 14 in the Annals of Neurology, in which he and his colleagues analyzed records on more than 8,000 people, most of them older than 60, who have been monitored over time at any one of about 30 Alzheimer's centers nationwide. Postdoctoral scholar Andre Altmann, PhD, was the lead author.

The records were stored in two large, publicly available repositories. In one, the researchers analyzed clinical assessments of 5,000 people whose test results were normal at the outset and 2,200 people who had initially showed signs of mild cognitive impairment. In both groups, being an ApoE4 carrier increased the likelihood of Alzheimer's disease, as expected. But a closer look revealed that among those who initially tested normal, this increased risk was only marginal for men, whereas women who carried the ApoE4 variant had close to twice the likelihood of progressing to mild cognitive impairment or Alzheimer's disease as those who didn't.

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Gene variant puts women at higher risk of Alzheimer's than it does men, study finds