2023 Sex and Gender in Alzheimer’s (SAGA) Grant (SAGA)
Molecular signatures of sex-biased cognitive trajectories in a primate
Do sex hormones influence cognition and Alzheimer’s-like symptoms in primates?
Agnes Lacreuse, Ph.D.
University of Massachusetts
Amherst, MA - United States
Background
According to the 2023 Alzheimer’s Association Facts & Figures report, of the more than 6.5 million Americans with Alzheimer’s, nearly two-thirds are women. However, the reasons underlying sex differences in Alzheimer’s remain unclear. Some research suggests that hormones, such as testosterone and estrogen, may impact cognition and the development of Alzheimer’s.
Cognition is shaped by many factors, including both social and environmental factors. Therefore, can be hard for researchers to determine what contribution of Alzheimer’s is strictly due to sex compared to molecules and hormones linked to sex. For this reason, some researchers use animal models to reduce social and environmental influences on the development of Alzheimer’s. Some nonhuman primates, including common marmosets, have brain structures that are similar to humans and also develop Alzheimer’s-like cognitive impairment as they age. Research shows that common marmoset females also have earlier and more rapid cognitive decline than males.
Research Plan
Dr. Lacreuse will use brain tissue from aged common marmosets, which had cognitive assessments preformed. They will study proteins in the brain responsible for recognizing difference sex hormones, such as the estrogen receptor and the androgen receptor (which testosterone interacts with). They will examine the extent to which those genes were turned on or off in males versus females and whether the gene activation correlates with cognitive data. They will also test for markers of Alzheimer’s in each brain sample. Additionally, using existing blood samples from the animals, they will measure sex hormones and other blood-based markers of Alzheimer’s.
Impact
The results of this study may help understand the biological mechanisms that put females at higher risk for developing Alzheimer’s.