Leah Conrad graduated from Randolph-Macon College in 2023 with a BA in behavioral neuroscience and is now a PhD candidate in brain and behavior in Natalie Tronson’s lab at the University of Michigan. Using a mouse model, Leah researches how oral contraceptive exposure and neuroimmune activity interact to confer resilience against Alzheimer’s disease. Her research interests span neuroendocrinology, neuroimmunology, and reproductive biology. After finishing her PhD she plans to do a post-doctoral fellowship before pursuing an academic career. Outside of the lab, she teaches an undergraduate course titled “The Neurobiology of Alzheimer’s Disease” and she especially enjoys hanging out with her cat Junie B.
Abstract: Alzheimer’s disease and neuroimmune activity in a mouse model of oral contraceptive exposure
Women represent two-thirds of Alzheimer’s disease diagnoses (AD) which emphasizes the importance of studying sex-dependent factors underlying this discrepancy. Previous studies show that exposures to estrogen across the lifespan, including pregnancy, hormone therapy, and oral contraceptive (OC) use, are associated with decreased risk for AD. Here, we examine how OC use may act as a resilience factor to delay AD-related pathologies including neuroimmune activation and amyloid beta (Aβ) plaques. We have previously shown that after immune challenge, OC- treated mice show decreased cytokines in the dorsal hippocampus and prefrontal cortex. This suggests that OCs may increase resilience against AD via modulation of neuroimmune processes. Currently, we aim to identify interactions between OCs and neuroimmune signaling in the development of AD. We hypothesize that OC treatment would slow AD-associated behavioral changes and pathologies including aggregation of Aβ plaques and aberrant microglial activation in a mouse model of AD. Nine-week-old female APP/PS1 mice drank daily ethinyl estradiol (EE, 0.02μg) and levonorgestrel (LVNG 0.75μg) in 10% sucrose until reaching 5.5-7 months of age before undergoing cognitive behavioral testing. APP/PS1 mice showed impaired memory as compared to wild type mice on the Context Fear Conditioning (CFC) task. Additionally, plaque count increased with age in sucrose treated APP/PS1 animals but not in EE+LVNG treated 5.5-7-month-old animals. OCs may decrease AD pathology development which may be attributed to differences in microglial function and activation states. Together, this work emphasizes how hormonal states can interact with risk and resilience factors like neuroimmune dysregulation to confer resilience against long term disease states.