Gene Variant ApoE-4 Possible Key Why More Women Get Alzheimer’s Than Men


Scientists had a long-standing assumption that a higher percentage of women than men get Alzheimer’s disease simply because they tend to live longer than men, but new research suggests that the loss of estrogen as women age, combined with some women having the gene variant ApoE-4, could be a possible key to the wide discrepancy in the rates. Women who reach age 65 have a one in six chance of developing Alzheimer’s disease during the rest of their lives. Men, by comparison, who make it to age 65 have a one in 11 chance of getting the disease.

There are probably multiple factors involved with getting Alzheimer’s disease, but a certain gene variant, ApoE-4, is looking more and more like a major culprit, along with the loss of estrogen that women experience as they get older.

While University of Southern California professor Roberta Diaz Brinton points out “that age is the greatest risk factor for developing Alzheimer’s disease,” that, alone, is not enough to explain why two-thirds of the Americans with the disease are women. Brinton decided to do research to find out if menopause plays a factor in why more women in America get Alzheimer’s disease than men.

Brinton the changes that menopause cause in the brains of women. Research that she and others have done indicates that the metabolism of the brains of women is regulated by estrogen and the hormone acts to produce energy for the brain to cognitively function better. As estrogen gets depleted when women enter menopause, the brain must rely on other, less efficient, ways to fuel itself.

She compares the reliance of the brain on estrogen and the loss of the homrone being a contributing factor to getting Alzheimer’s disease to diabetes, stating that “It’s like the brain is a little bit diabetic.”

There is a difference not only in how many more women get the disease than men in America, but also a difference in how quickly the disease worsens once it is diagnosed in women compared to men. Scans of the brains of women and men who have Alzheimer’s disease have shown that certain area of the brain show a faster rate of shrinking in women than in men.

Women who have the gene variant ApoE-4, according to an analysis by Stanford University researchers of the records of over 8,000 people, have twice as much of a chance to develop Alzheimer’s disease than women who do not possess the gene variant. Though no one is sure why this is the case, a theory has been developed that it might have to do with how the gene variant interacts with estrogen.

There has been conflicting research done about the risks and benefits of estrogen replacement, but later research has shown that if estrogen is replaced at around the time women undergo menopause there is not the possible increased risk of dementia that such hormone replacement might cause in women over 65.

Estrogen loss combined with the possession of gene variant, ApoE-4, is looking more and more like a key to unraveling the mystery of why two-thirds of the Americans who have Alzheimer’s disease are women. While the fact that women, on average, tend to live longer than men is definitely a big factor, women who have the gene variant ApoE-4 are at a 200 percent higher risk of developing Alzheimer’s disease. With men who possess the same gene, the risk was a bit higher, but nowhere close to 200 percent higher. More research still needs to be done to fully understand why such a huge difference exists.

Written and Edited By Douglas Cobb

CBS News: Scientists explore why most Alzheimer’s patients are women
The Daily Star: Why do more women than men have Alzheimer’s?
NY City News: Alzheimer’s diagnosis more in Women than in Men: Study
Photo Courtesy of Susumu Komatsu’s Flickr Page – Creative Commons 2.0

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