Women are twice as likely to suffer from Alzheimer’s as men. Scientists have figured out why

Experts have long known that women are at a greater risk of developing Alzheimer’s disease. They’re twice as likely to be affected as men.

Now scientists say they may be on their way to understanding why that’s the case – pinpointing two stark differences between men and women. Firstly, women have different chromosomes than men. They also undergo menopause: a process that occurs when a woman’s reproductive hormones naturally decline starting in her 40s and 50s.

One in three older Americans dies with Alzheimer’s, or another dementia, according to the Alzheimer’s Association. Almost two-thirds of Americans with Alzheimer’s disease are women.

“Epidemiologically, we see that for almost all neurological diseases, there are differences in how many biological women and men are affected,” Anna Bonkhoff, resident and research fellow in neurology at Harvard Medical School and Mass General Brigham, explained in a recent interview. “There’s a tendency, for example, in [multiple sclerosis] and migraine for more females to be affected, while it’s the contrary for brain tumors and Parkinson’s.”

“Just based on these numbers, you get the feeling that something needs to underlie these differences in terms of the biology,” she added.

Looking inside the body, while women have two “X” chromosomes, men have an “X” and a “Y.” Chromosomes are thread-like structures of DNA inside our cells that carry hundreds or even thousands of genes. Genes determine a person’s physical characteristics. Differences between genes held on the X and Y chromosomes may give women an increased chance of developing Alzheimer’s disease.

Recent research has shown that genes on the X chromosome are related to Alzheimer’s disease, including that women with Alzheimer’s live longer than men with the disease due to their second X chromosome.

“A lot of genes for the immune system and regulating brain structure are located on the X chromosome, so the dosages differ to certain degrees between men and women. That seems to have an effect,” said Bonkhoff.

Women’s different dominant hormones — such as estrogen, which acts on the brain — could also play a role.

“Menopause is part of the puzzle, probably one of the bigger ones,” Bonkhoff said. “I’m not saying it’s the only one — aging is relevant by itself, and there’s a lot of interesting research looking at what aging does to the immune system that seems to have implications for cognitive changes.”

During menopause, when ovaries stop producing estrogen and progesterone, some women turn to hormone replacement therapy. The practice offers relief for symptoms of lower hormone levels in menopause such as hot flashes. But for some women it may increase their risk of dangerous medical conditions, including heart attacks, strokes, breast cancer, blood clots and gall bladder disease, according to the Centers for Disease Control and Prevention.

Women who received hormone replacement after age 70 also have significantly higher levels of the protein known as “tau,” according to Rachel Buckley, associate professor of neurology at Harvard Medical School. The accumulation of tau is a hallmark of Alzheimer’s disease. They also suffered higher cognitive decline.

Buckley published those findings last March in the journal Science Advances. But further research is needed to understand these associations.

“We work with a lot of secondary data that already exists, and that’s great but there are limitations to what we can do with it,” Buckley said. “We’re trying to see if we can set up a new study design where we can really look at the time of menopause, what is changing in the blood, what is changing in the brain, what is changing in cognition, and how that might be associated with later life risk.”