Why do so many more women have Alzheimer’s than men?

According to the Alzheimer's Association, one in six women over the age of 65 are at risk for developing Alzheimer's. That's compared to a one in eleven chance of developing the disease for men of the same age. Put another way, two-thirds of all Americans with Alzheimer's are women. But why?

The simple answer — though the science behind it is far from simple — may be that women’s brains age differently than men’s do.

“When you look at the risk for developing Alzheimer's disease, men have a bit of an increased risk early, around age 65 or so — more than women. But then women take over the risk in their seventies,” says Roberta Diaz Brinton, a professor of pharmacology and pharmaceutical sciences at the University of Southern California.

There is a common notion that women are more likely to develop Alzheimer’s simply because they live longer than men and have more time to develop symptoms. But Brinton says it’s much more complicated than that.

“It is more likely the way that [women] age that puts them at risk, not the four years longer that they live,” Brinton says. Specifically, she believes, it’s the way women’s brains change as they go through perimenopause and menopause that leaves them at a higher risk for Alzheimer’s than men.

Perimenopause is a decline in estrogen levels that leads to certain physical changes. But Brinton says it's also a neurological transition that alters the brain’s ability to generate sufficient energy to keep all of its systems working well.

“Most women will transition through perimenopause and menopause quite well — and then there will be a proportion of women who will begin to experience neurological symptoms that are seemingly unrelated to the reproductive change that's happening,” Brinton says. “Those neurological symptoms can manifest themselves as decline in cognitive function, particularly short-term memory function.”

There may also be a link between estrogen decline and a gene called ApoE4. ApoE4 occurs in both women and men, but a 1997 study found that carrying one copy of ApoE4 quadruples a woman's risk of developing Alzheimer’s; men with one copy of the ApoE4 gene showed no increased risk compared to men without it.

The ApoE4 gene may also play a part in the so-called beta-amyloid hypothesis. Beta-amyloid is a fragment of a larger protein called the amyloid precursor protein, which occurs throughout the body. The build-up of beta-amyloid deposits in the brain is considered one of the main causes of Alzheimer’s.

ApoE4 is involved in clearing beta-amyloid from the brain, but it doesn’t do a very good job, Brinton says. Its lack of effectiveness could be one of the causes of beta-amyloid "clumping" that is believed to interfere with synapses in the brain and lead to cognitive dysfunction.

To counteract some of these disruptive reactions in the brain, Brinton and her colleagues are developing a "regenerative therapeutic" for early-stage Alzheimer's disease. It's based on a molecule called allopregnanolone, which she says promotes the regeneration of the brain and the generation of new neurons. Pregnant women produce it in abundance, and scientists believe it plays a key role in fetal brain development.

Yet even while such work is being done, cures and preventative treatments for Alzheimer’s disease continue to elude researchers. One thing is becoming clear, though: Men and women do age differently, and future studies will need to look at each sex differently when it comes to Alzheimer's.

This article is based on an interview that aired on PRI's Science Friday with Ira Flatow.