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New Study Explores Why Alzheimer’s is Worse for Women

The new study will be co-led by Sarah Banks (left), PhD, a neuropsychologist at UC San Diego Health and professor in the Department of Psychiatry at UC San Diego School of Medicine and Erin Sundermann (right), PhD, an associate professor in the the Department of Psychiatry at UC San Diego School of Medicine.
Photo by UC San Diego Health Sciences

Researchers from University of California San Diego have received $5.2 million from the National Institutes of Health to piece together a puzzling problem in medicine: determining why women are more likely to get Alzheimer’s disease and why the disease is more aggressive in women than in men. The five-year project will measure brain inflammation and circulating sex hormones in women at risk for Alzheimer’s and relate these measures to changes in cognitive function and accumulation of protein deposits in the brain. The project will be co-led by Sarah Banks, PhD, a neuropsychologist at UC San Diego Health, and Erin Sundermann, PhD, an associate professor in the Department of Psychiatry at UC San Diego School of Medicine.

By better understanding what drives sex-based differences in Alzheimer’s, the researchers hope to help identify therapeutic targets and lifestyle interventions for the disease that are tailored specifically for women and can help reduce the sex-based disparities observed in Alzheimer’s disease. Alzheimer’s disease and other forms of dementia are the seventh leading cause of death in the United States.

Women are disproportionately affected by Alzheimer’s disease, accounting for nearly two-thirds of total cases according to the Alzheimer’s Association. One reason for this disparity is that women live longer on average and age is the biggest risk factor for developing Alzheimer’s. However, scientists who study Alzheimer’s disease are now turning their attention to other sex-based differences in the disease that can’t be explained by life expectancy.

The brains of people with Alzheimer’s disease are characterized by abnormal protein deposits, including a protein called tau. Women with Alzheimer’s have more of these protein deposits than men. Alzheimer’s is also associated with inflammation in the brain, and women generally experience stronger inflammatory responses than men.

Another factor that may drive sex-based differences in Alzheimer’s disease is hormones. Testosterone, a sex hormone with higher levels in men, shows some evidence of a protective effect against tau pathology. Additionally, some scientists hypothesize that loss of estrogen during menopause may contribute to the early development of the disease.

While there is a growing body of evidence suggesting that Alzheimer’s is expressed differently in women, scientists don’t yet understand the specific pathways and risk factors driving this disparity. With the support of the new grant, the researchers will attempt to shed light on this subject by studying the brains of 100 older women at risk of Alzheimer’s disease from the Women Inflammation and Tau Study (WITS). This state-funded pilot study was launched during the early stages of the pandemic, and the new federal grant will allow the researchers to expand upon their work and recruit additional participants.

The researchers will measure the degree of inflammation in the brain and the levels of sex hormones circulating in the blood. By comparing these measurements to changes in cognitive function and the accumulation of protein deposits in the brain, the researchers hope to identify quantifiable relationships between these factors. The researchers will also assess the role of modifiable lifestyle factors, such as physical activity and diet, in the progression of tau pathology.

Miles Martin