Alzheimer's disease (AD) is a chronic neurodegenerative disease and a major cause of dementia. While early symptoms include short term memory loss, as the disease advances, symptoms progressively worsen and include cognitive decline, disorientation, and ultimately loss of body function and death. The disease involves accumulation of plaques in the brain, which are characterized by the deposition of a protein called amyloid-? (A?). Relatively recent research has shown that the immune system is an important component of AD. Speci?cally, 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 can also be critical in AD. Understanding microglia in AD, is therefore necessary, 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 speci?c molecule, a growth factor and cytokine called IL-3 is protective in AD. We show that a cluster of immune cells called astrocytes inhabiting speci?c locations of the brain produce IL-3, which then activates microglial cells, instructing them to remove the harmful amyloid-? (A?) plaques. In the absence of IL-3, however, microglia are unable to ?nd amyloid-? (A?) plaques, which worsens disease. IL-3, therefore, might be an important therapeutic in AD. This application will focus on the role of microglial-astrocyte communication in AD.
Microglia are a special kind of macrophage that resides in the brain. As part of this application, we will test the role of microglia in development of Alzheimer's Disease. Specifically, we will ask whether a growth factor made by astrocytes educates microglia to remove beta-amyoid, the build-up of which is a central feature of Alzheimer's.
