Investigations into the Relationship Between Menopause and Alzheimer’s Disease Pathology in a Mouse Model with Ovarian Follicle Depletion

Alzheimer’s Disease (AD) currently affects about 6.9 million Americans, with over two-thirds of those individuals being women. Interestingly, changes in the brain indicative of AD coincide with the onset of menopause. Post-menopausal women have significantly higher levels of AD pathologies, including amyloid beta and hyperphosphorylated tau, than pre-menopausal women. To investigate the relationship between AD pathologies and menopause, we induced menopause-like state in an AD mouse model, APP/PS1, by treatment with 4-vinylcyclohexene diepoxide (VCD) to accelerate ovarian follicle depletion. To monitor the transition to menopause, vaginal lavages and cytology was performed to determine if mice reached anestrous. Both female APP/PS1 mice and controls reached anestrous and tissues were evaluated for AD related changes. Female APP/PS1 mice treated with VCD had significantly reduced levels of AB-42 in the hippocampus. Overall, this study demonstrates the utility of using VCD in AD study to investigate the association with menopause. These studies could further research into novel biomarkers and therapeutics for women with AD.