Stress increases Alzheimer’s risk in female mice but not males – Washington University School of Medicine in St. Louis

Women are about twice as likely as men to be diagnosed with Alzheimer’s disease. Part of it is age. In the United States, women outlive men by five to six years, and older age is the greatest risk factor for Alzheimer’s disease. But that’s not all. Alzheimer’s researchers continue to look for reasons why women are at higher risk for the fatal neurodegenerative disease.

Stress may be one such reason. A study by researchers at the Washington University School of Medicine in St. Louis shows that the effects of stress on the brain differ by gender, at least in mice. In stressful situations, levels of the Alzheimer’s disease protein amyloid beta rise sharply in the brains of women, but not men. We identified the molecular pathways that are activated and showed that they are responsible for diverse responses to stress.

The findings, published May 2 in Brain, add to the growing body of evidence that sex is important in health and disease. Scientists have discovered differences between men and women that can influence how men and women respond to efforts to prevent and treat chronic diseases, from cancer to heart disease to arthritis.

“How women respond to stress and how men respond to stress are important areas of research that have implications not just for Alzheimer’s disease but for other conditions,” said co-corresponding authors. I’m here. Dr. Kara M. Yuede, Associate Professor of Psychiatry. “In recent years, the National Institutes of Health (NIH) has made understanding gender differences in medicine a priority. Stress is one area where men and women clearly differ. , suggest that it may be more beneficial for women than men in terms of lowering the risk of Alzheimer’s disease.”

Stress falls into the category of socioeconomic risk factors, along with factors such as depression and social isolation, which together are estimated to account for an estimated 8% of the risk of developing Alzheimer’s disease. However, that risk calculation does not take gender into account. Women consistently report higher levels of stress than men, and stress affects women’s bodies in different ways than men, including cardiovascular health, immune response, and other issues.

Corresponding author Dr. John Silito, Associate Professor of Neurology. Yuede; lead author Hannah Edwards, a graduate student in her Cirrito lab, says that stress can also affect women’s brains differently than men’s, and that these differences contribute to gender imbalance in Alzheimer’s disease. reasoned that it might help explain the

The researchers measured the levels of amyloid beta (a key protein in Alzheimer’s disease) in the brains of the mice every hour for 22 hours, starting eight hours before the mice became stressed. The experience stressed male and female mice equally, as measured by levels of stress hormones in their blood.

In female mice, amyloid-beta levels were significantly elevated within the first 2 hours and remained elevated until the end of the monitoring period. In male mice, brain amyloid levels were globally unchanged, although about 20% of them showed a delayed, weak increase in amyloid levels.

Further experiments revealed that the differences resulted in cellular stress response pathways in brain cells. Stress triggers the release of a hormone known as corticotropin-releasing factor. Neurons in female rodents take up stress hormones, triggering a series of events that result in elevated levels of amyloid beta in the brain. In contrast, male rodent neurons lack the ability to uptake stress hormones. It is not known whether there are similar sex differences in how human neurons take up stress hormones.

“In both mice and humans, there are fundamental biological differences between men and women in the way they respond to stress at the cellular level,” Cirrito said. I don’t think it’s the only factor that causes it, there are many other differences between men and women that definitely contribute in some way, such as hormones, lifestyle, and other ailments. I think it’s very likely that stress is driving one aspect of this gender difference.”