Neuroimmune Consortium: Mechanisms Mediating Microglia Sensing of Peripheral Inflammation

Several lines of evidence support the concept that sources of inflammation outside of the brain contribute to the development of Alzheimer’s disease (AD). This relationship could account for various inflammatory diseases of aging being risk factors for AD, including diabetes, coronary artery disease, and rheumatoid arthritis. However, the mechanisms by which the brain senses peripheral inflammatory signals are poorly understood. In this application, we propose to apply a combination of genetics, state-of-the-art imaging methods, and analysis of regions of the genome that regulate cell function to characterize the temporal and spatial responses of immune cells in the brain to a specific peripheral inflammatory stimulus and to assess further the consequences of these immune cell responses on the other cell types of the brain. These studies will fill major knowledge gaps in understanding how the brain responds to peripheral inflammation and provide insights into the question of whether targeting peripheral inflammation could be beneficial in the prevention and treatment of AD.