Project 419344

Alzheimer's disease (AD) is a disease that results in the progressive loss of cells in the brain, in particular in an area important for the formation of new memories, called the hippocampus. Women are more likely to be diagnosed with AD and show greater brain pathology and memory loss with the disease than men. In addition, women are more likely to develop Alzheimer's disease especially when they have certain genes (APOEe4) and a previous history of multiple pregnancies. This project aims to characterize the aging female brain and how is affected by reproductive experience (pregnancy) and genetics (APOEe4 status) under hormone therapy, immune, and metabolic (diet) challenges. Menopause is associated with dramatic changes in hormone levels and with cognitive decline and certain hormone therapies (HTs) positively affect cognition depending on timing and genotype. Our research shows that the sensitivity of the female brain to estrogens is altered with past parity to affect neuroplasticity and immune signalling. The goal of this proposal is to study the effects of parity and genetics on aging in the female brain exposed to hormone therapies, immune and metabolic challenges in preclinical models. This work will determine how physiological challenges faced by females during aging interact with motherhood and genetics can affect brain aging. It is clear that tailored treatment based on sex, genetics, and possibly reproductive history need to be developed to best treat individuals at risk to develop AD.