Microglia are the brain’s immune cells and express multiple Alzheimer’s disease (AD) risk genes. Understanding the impact of these risk genes on microglia is essential to identify how disease is initiated and progresses. Recently, it has been shown that peripheral inflammation is a major component of AD pathogenesis, but we don’t know how microglia respond to this specific inflammation. In this study, we will use stem cell models to understand how AD genetic risk alters the response of human microglia to peripheral inflammation. This project will identify new pathways by which microglia become dysfunctional in disease, and highlight how they impact other brain cells and disease progression.