Genome-wide association studies have identified >20 loci with high Alzheimer’s Disease (AD) susceptibility, many of which overlap with genes highly expressed in microglia. These findings highlighted the role microglia play in protein aggregation and neurodegeneration in AD pathology. Microglia are the resident immune cells of the central nervous system (CNS). Actions of microglia are stage and state dependent, regulated by microglial surface receptors and proteins. They prune synapses during development, uptake cellular debris in the homeostatic brain, and engulf pathogenic materials in the diseased brain. In Alzheimer’s Disease (AD), microglia receptors detect aggregated beta-amyloid (Aβ) and secrete signals to uptake the protein. Disease-state microglia also trigger inflammation in the CNS and display dysregulated phagocytic activity, engulfing synapses and damaging neuronal integrity.
My research aims to identify novel regulators of microglial phagocytosis relevant to Alzheimer’s Disease.