Age is the most important risk factor for Parkinson’s Disease (PD), followed by sex, with a higher risk in males. Studies show that brain inflammation occurs early in the disease and persists throughout its course. As such, inflammation is likely to contribute to the disease. In the brain, the main immune cell generating an inflammatory response is microglia. Experimental data points toward genetic and hormonal sex differences in microglia influencing the brain inflammatory response. However, as most of our knowledge on how microglia generate inflammation in the brain of PD patients comes from animal studies, reports looking at human microglial function are much needed. We and others have developed methods to be able to convert patient cells from accessible sources, such as skin biopsies, to brain cells. Building on this previous work, we will now study how aging influences the sex-specific microglial response using microglia derived from skin cells of PD patients. The results of this study will provide important insight into sex differences in PD and the potential for sex specific therapies. This project uses a unique and novel human model system to also address the contribution of aging to PD-related neuroinflammation. Understanding the molecular mechanisms of how age and sex influence the immune response in PD will facilitate the identification of new drug targets.