APOE Consortium: Cell Autonomous Roles of Protective APOE Variants in Microglia in Response to Amyloid Pathology

Alzheimer’s disease (AD) is the leading cause of dementia, and variants of the APOE gene are the strongest genetic predictors of risk. While certain variants, like APOE4, increase the likelihood of developing AD, others, such as APOE3 Christchurch, appear to protect against it. This project aims to understand how different APOE variants affect the response of brain immune cells called microglia to amyloid plaques. By studying both human and mouse models, we will investigate whether introducing protective APOE variants in microglia alters their response to amyloid and improves disease outcomes in AD models. Our goal is to identify new mechanisms that explain how APOE variants in brain immune cells reduce AD risk, with the ultimate goal of developing new therapeutic strategies based on these mechanisms.