Relatively recent research has shown that the immune system is an important component of Alzheimer’s disease (AD). Specifically, interspersed throughout the brain among and between the neurons are immune cells called microglia that reside in the brain throughout life and participate in many normal functions, but that also can be critical in AD. Understanding microglia in AD is therefore vital, as it may uncover previously unknown pathways by which the immune system promotes or protects against AD. A powerful strategy to delve into microglial function involves identifying the key molecules that control microglial development, survival and behavior. For this application, we have generated preliminary data suggesting that a specific molecule, a growth factor and cytokine called IL-3, is protective in AD. We show that a cluster of immune cells called mast cells inhabiting specific locations on the periphery of the brain produce IL-3, which then activates microglial cells, instructing them to remove harmful amyloid beta plaques, the accumulation of which is thought to lead to the development of the disease. In the absence of IL-3, however, microglia are unable to find amyloid beta plaques, which worsens disease. IL-3, therefore, might be an important therapeutic in AD. This application will elucidate the role of IL-3 in animal models of AD.