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2017 Grants - Town
Brain Sexual Dimorphism and Aging Interact in Development of Alzheimer’s Disease
Terrence Christopher Town, Ph.D.
University of Southern California
Los Angeles, California
2017 Sex and Gender in Alzheimer’s (SAGA) Grant
Do inherent sex differences in brain structure and hormonal changes during aging interact to affect the development of Alzheimer’s?
Although the brains of females and males are mostly similar, there are certain regions and features of the brain that differ according to sex (sexual dimorphism). These differences occur as the brain is forming and are considered “developmental effects.” Additionally, increasing evidence suggests that women may have higher risk of Alzheimer’s disease than men. Some lines of research suggest that the increased risk among women may be due to some of these developmental differences in brain structure. Other lines of research suggest that declines in the hormone estrogen during aging in women could account for the increased risk. It is possible that both of these factors, estrogen and developmental differences, contribute and may even interact in ways that lead to increased risk of Alzheimer’s disease in females.
Terrence Christopher Town, Ph.D. and colleagues will study how sex differences in the brain, either due how the brain develops differently between males and females, or due to changes in estrogen levels during aging, may impact the development of Alzheimer’s disease. For these studies, the researchers will use a novel animal model, which for the first time mimics nearly all of the brain changes associated with Alzheimer’s disease. These genetically-altered rats develop plaques and tangles, neuroinflammation, loss of nerve cells and memory problems. Dr. Town’s team will study male and female Alzheimer’s-like rats as they age and determine if there are sex-related differences in their brain structure and function. They will also examine if aging female rats show accelerated disease progression and determine if estrogen treatment can help prevent these changes.
This research will help answer key questions on how sex differences related to biology versus aging influence the risk for Alzheimer’s disease. A better understanding of these mechanisms can inform the development of new strategies to diagnose and treat Alzheimer’s disease in both men and women.