Carlos Cruchaga, PhD, Washington University School of Medicine, St Louis, MO, comments on unanswered questions regarding the role of microglia in Alzheimer’s disease. Data has emerged over recent years that emphasizes the complex nature of microglia activity, suggesting they play disparate roles in the development and progression of Alzheimer’s pathology. Genome wide association studies have spotlighted the role microglia in the pathogenesis of Alzheimer’s, with the major of risk genes highly (or even selectively) expressed by microglia. Some studies indicated that activated microglia may be protective in disease development and early-stage disease, as impaired activity has been associated with increased disease risk. However, it is also clear that microglia proliferation and hyperactivation is prominent later in Alzheimer’s disease, shown to cause synapse loss, neuroinflammation, and astrocyte activation. Microglia are highly dynamic and interactive and thus, many aspects of their context-specific and disease-stage-specific activity remains controversial. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.
