Women carrying a certain gene variant are more likely than men with the same gene variant to develop Alzheimer's disease, a new study has found.
Researchers from Stanford University School of Medicine analysed 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 centres in US.
The records were stored in two large, publicly available repositories. In one, the researchers analysed 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.
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In both groups, carrying a copy of a gene variant called ApoE4 increased the likelihood of Alzheimer's disease, as expected, researchers said.
However, 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.
"Our study showed that, among healthy older controls, having one copy of the ApoE4 variant confers a substantial Alzheimer's disease risk in women, but not in men," said Michael Greicius, assistant professor of neurology and neurological sciences and medical director of the Stanford Center for Memory Disorders.
The second repository holds imaging data and measurements of several biochemical substances from spinal fluid that can serve as useful biomarkers of impending mild cognitive impairment and eventual Alzheimer's disease.
Analysis of 1,000 patients' records from this database not only confirmed ApoE4's differential effect on women versus men, but also yielded clues that may help investigators begin to explore, and perhaps someday explain, the molecular mechanisms linking ApoE4 to Alzheimer's disease, Greicius said.
The ApoE gene is a recipe for a protein important for shuttling fatty substances throughout the body.
This is particularly important in the central nervous system, as brain function depends on rapid rearrangement of such fatty substances along and among nerve cell membranes.
Numerous studies going back to the early 1990s have confirmed that ApoE4 is a key risk factor for Alzheimer's disease, with a single copy of ApoE4 increasing that risk twofold or fourfold. Carrying two copies confers 10 times the risk of Alzheimer's.
The new research was published in the journal Annals of Neurology.
