Interactions of Pregnancy and Menopause on Alzheimer’s Disease Outcomes

The goal of this project is to use a mouse model to determine how pregnancies and menopause interact to affect cognitive function, stress-related behaviors, and neuropathology associated with AD.

Women are disproportionately affected by Alzheimer’s disease (AD) relative to men. Life course factors unique to women, including pregnancy and menopause, likely contribute to female vulnerability, although how these two factors interact to affect AD-related outcomes is unknown. We propose to use a mouse model of AD to determine how the combination of pregnancy and menopause impacts cognitive/behavioral functions and AD-associated neuropathology.

The primary innovation of this proposal lies in developing a mouse model for female life course risk factors for AD, including pregnancies and menopause. Previous studies have independently assessed effects of pregnancy and menopause; however, this will be the first to determine interactions of these critical life factors on AD-related behavioral outcomes and neuropathology.

The greatest impact of this research lies in the potential for developing personalized therapeutic approaches for Alzheimer’s disease (AD). These studies are designed to reveal specific life course factors, and combinations of these factors, that sex-specifically impact AD-related outcomes. Information from this study thus represents a key starting point that can ultimately lead to clinical studies that may be geared toward individualized hormone treatment regimens designed to mitigate the development of AD-related neuropathology and cognitive decline.