Alzheimer’s disease (AD) emerges late in life, but its origins may trace back to how the brain’s own immune cells are established before birth. These cells, arising from the yolk sac during embryogenesis, settle in the brain and serve as lifelong caretakers of brain health. Yet, it remains unclear how early-life inflammation and genetic risk factors such as APOE4 shape the development and long-term behavior of these cells, potentially influencing vulnerability to AD. This project employs complementary human stem cell– based platforms to model how yolk sac–derived immune cells develop, migrate, and interact with brain tissue. By studying the impact of inflammatory signals and APOE4, including changes in cellular migration, integration, and functional maturation, these studies aim to investigate how early immune programming contributes to AD pathology later in life. Ultimately, this project could reveal novel mechanistic insights and potential therapeutic strategies targeting immune cells as an early intervention to prevent AD.
