Could the effects of stress on women be a reason why more women have Alzheimer’s disease than men?

    By Kathleen Berger, Executive Producer for Science and Technology

    Stress that’s not addressed or treated can lead to many health problems.

    “We’ve known in several disease conditions and disorders that stress makes things worse,” said Carla M. Yuede, PhD, associate professor of psychiatry at Washington University School of Medicine in St. Louis.

    Yuede is focused on how stress relates to the development of Alzheimer’s disease. Studies show that women are about twice as likely as men to be diagnosed with Alzheimer’s disease. So, could stress be a reason why?

    “Over the last probably five or six years, the realization that Alzheimer’s disease was more prevalent in females, even when you correct for the fact that females live longer,” Yuede explained.

    To get answers, Yuede collaborated with John Cirrito, PhD, and his lab. Cirrito is a professor of neurology at Washington University School of Medicine. The research team examined levels of amyloid beta in the brains of mice, a key Alzheimer’s protein.

    “It (amyloid beta protein) starts to aggregate and forms clumps that build up is what’s called plaques in an Alzheimer’s brain. And that can start 15 to 20 years before the first symptoms of Alzheimer’s even begins,” explained Cirrito.

    But how does stress relate to the development of amyloid plaques in the brain?

    “About 15 years ago, we were looking at the effects of stress, specifically on amyloid beta pathology, in an Alzheimer’s disease mouse model and found that stress did, in fact, make the amyloid beta plaques that develop in the brain worse in this model. We did not look at the difference between males and females,” said Yuede.

    With more information about Alzheimer’s disease emerging, Yuede and Cirrito decided to take a deeper dive into their previous research.

    “We went back to our stress studies to look at the differences between males and females in that specific model. And we actually found that female mice, when they’re stressed, have a much greater increase in amyloid beta that lasts a lot longer than the response we would see in male mice. In male mice, we saw almost no response at all. Some mice did respond, so it’s not 100%,” said Yuede. “All females, all males do not respond. But it was a lot more striking in female mice than in males.”

    Further experiments revealed that the difference comes down to a cellular stress response pathway in brain cells.

    “There’s a fundamental signaling difference between males and females,” said Cirrito.  “A lot of this is driven by what’s called the corticotropin releasing factor.”

    More studies are needed to see if stress and anxiety treatments could prevent or treat the development or progression of Alzheimer’s Disease.

    “Effects on that stress by using medicines, is that beneficial? Can you prevent this change in amyloid levels? There are also other things that go on in the brain,” Cirrito explained. “There’s a protein called tau that builds up in Alzheimer’s disease. We have some data to suggest that stress affects tau as well. So those are follow-up studies, and then what else is going on in the brain. Inflammation would be another good factor to look at.