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2020 Alzheimer's Association Research Fellowship (AARF)

Sex, tau accumulation, and the role of menopause in AD pathogenesis

Why are women more susceptible to Alzheimer’s than men?

Rachel Buckley, Ph.D.
Massachusetts General Hospital
Boston, MA - United States


More women than men have Alzheimer’s or other dementias. According to the 2020 Alzheimer’s Facts and Figures report, of the more than 5 million Americans aged 65 and older with Alzheimer’s, two-thirds of these are women. However, the primary drivers of this difference are unknown. Studies show that women with Alzheimer’s brain changes (such as build-up of beta amyloid protein into plaques, a hallmark brain change in Alzheimer’s) may have higher levels of abnormal tau in the brain than men. Abnormal tau can form tau tangles in the brain, which is one of the hallmark brain changes observed in Alzheimer’s, frontotemporal dementia, Pick’s disease, Parkinson’s disease and over 20 other brain diseases. 

Dr. Rachel Buckley and colleagues  will aim to better understand  sex differences in the risk for Alzheimer’s by specifically looking at the higher rates of tau accumulation in women and its impact on cognitive performance.

Research Plan

Dr. Buckley and colleagues will leverage Positron Emission Tomography, (or PET) brain scan data from the Harvard Aging Brain Study. Using this data, Dr. Buckley’s team will determine whether there are differences in the amount of tau accumulation in the brains of men versus women. The researchers will further investigate if women with genetic risk factors for developing Alzheimer’s have differences in the levels of tau accumulation compared to men. Additionally, the researchers will study if cognitive function is impacted differently due to the various levels of tau accumulation in men and women. Finally, using data from the Harvard Aging Brain Study and the Framingham Heart Study, (with participants aged 35-90 years old) the researchers will investigate the impact of menopause on the levels of tau accumulation.  Dr. Buckley believes that an earlier age of menopause (associated with reduced exposure to sex hormones) could lead to higher levels of tau accumulation in the brains of women compared to men.


The study results may help inform our understanding of sex differences in Alzheimer’s risk. The results could be used to design future intervention strategies to reduce the risk of dementia for women and men.

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