More women than men get Alzheimer’s disease, in part because women tend to live longer than men and the chances of developing Alzheimer’s increases with age. But new research suggests there may be genetic reasons as well.
Researchers at Stanford University School of Medicine are reporting that women who carry the APOE-E4 gene, which increases the risk for Alzheimer’s, are more likely to develop the disease than men who have the same gene. More than one in seven people carries a copy of the APOE-E4 gene.
Everyone carries some version of the APOE gene, which plays a role in how cholesterol and fats are shuttled throughout the body. But certain variants of the gene affect Alzheimer’s risk. People who carry the APOE-E2 variant, for example, are less likely to develop Alzheimer’s, whereas those who carry the APOE-E4 variant are at increased risk.
Numerous studies going back to the early 1990s have confirmed that APOE-E4 is a key risk factor for Alzheimer's disease. A single copy of APOE-E4 increases that risk twofold to fourfold, whereas carrying two copies of the gene, one from each parent, confers 10 times the risk of Alzheimer's. While only about 15 percent of the general population carries the APOE-E4 gene, almost half of those with Alzheimer’s have the gene.
Still, carrying the APOE-E4 gene does not mean that you will develop Alzheimer’s. Many people who have the gene will never get the disease.
For the study, Stanford scientists sifted through medical data on more than 8,000 older men and women to see who carried the APOE-E4 gene and who subsequently went on to develop Alzheimer’s disease over the next three to four years. They also tracked who came down with mild cognitive impairment, a form of memory loss that sometimes progresses to full-blown Alzheimer’s.
Men who carried the gene were only slightly more likely to develop Alzheimer’s. But over the course of the study, women with the gene had close to twice the likelihood of progressing to mild cognitive impairment or Alzheimer’s disease as those who didn’t have the gene.
The fact that women tend to live longer than men explains only part of women's increased susceptibility to Alzheimer's. "Even after correcting for age, women appear to be at greater risk," said Dr. Michael Greicius, a study author and medical director of the Stanford Center for Memory Disorders. "Our study showed that, among healthy older controls, having one copy of the APOE-E4 variant confers a substantial Alzheimer's disease risk in women, but not in men."
The findings could offer clues to why more women than men develop Alzheimer’s and the role of the APOE gene in causing disease. It could also open up doors for the exploration of new drug treatments.
Already, many clinical trials for Alzheimer’s take APOE status into consideration. It’s possible that some therapies may be more effective in people who carry APOE-E4 or other gene variants, but more research is needed to determine why women should be affected differently than men.
Dr. Greicius noted that increasingly people are getting genetic tests that tell them whether they carry the APOE-E4 gene. “People come to me and say, 'I have an APOE-E4 gene, what should I do?'” he said. “If that person is a man, I would tell him that his risk is not increased much if at all. If it's a woman, my advice will be different."
Source: Andre Altmann, Lu Tian, Victor W. Henderson, et al: Sex modifies the APOE-related risk of developing Alzheimer disease. Annals of Neurology, April 14, 2014