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What could be drivers of Alzheimer’s that are similar and different in men and women?
Sarah Banks, Ph.D.
University of California
La Jolla, CA - United States
Background
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.
Studies also suggest that sex hormones, particularly testosterone may impact brain inflammation and abnormal tau. However, the biological mechanisms relating to sex-specific differences in how abnormal tau moves in the brain and impacts brain function is not yet clear. Dr. Sarah Banks and colleagues will study if there are sex-specific differences in how biological markers (biomarkers) of brain inflammation may affect tau levels over the course of the disease progression. In addition, Dr. Banks and her team will evaluate how the tau protein moves throughout the brain during disease.
Research Plan
To conduct their study, the researchers will recruit participants from the University of California San Diego Alzheimer’s Disease Research Center (ADRC) and the community resources associated with the ADRC Outreach and Education Core. Dr. Banks and colleagues will recruit 50 older women (aged 65-80) at risk for Alzheimer’s based on their age, a cognitive score that reflects mild cognitive impairment and a defined Polygenic Hazard Score (PHS) — which is a measure that analyzes small changes in genes in the DNA and in prior work is associated with increased presence of disease-related brain changes.
The researchers will analyze the testosterone and biomarkers for brain inflammation using blood and cerebrospinal fluid (CSF- the biological fluid surrounding the brain and spinal cord) samples from the participants. Dr. Banks and her team will also administer cognitive tests and brain scans to the participants. Using advanced statistical techniques, the researchers will study a) whether higher levels of biomarkers of brain inflammation impact abnormal tau levels and cognitive decline in women at risk for Alzheimer’s and b) whether testosterone levels impact the association between biomarkers for brain inflammation and movement of abnormal tau in the brain.
Furthermore, Dr. Banks and colleagues will study whether modifiable risk factors such as diet, physical activity and sleep, impact the levels of inflammation biomarkers in the brain as well as the movement of abnormal tau in the brains of these women. The researchers will continue to engage and follow these women for over a year, repeating these measurements in the participants to continue to monitor the association during disease progression between brain inflammation and abnormal tau.
Impact
The study results may inform our understanding of Alzheimer’s in women and men. Dr. Banks proposes to leverage funding from the National Institutes of Health (NIH) to expand her research to further address these important questions. If successful, these results could pave the way for future studies that could include sex-specific clinical trials and lifestyle interventions. The results could help develop specialized therapies for both men and women at risk for Alzheimer’s.
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