July 23rd, 2026
Microglia are innate immune cells resident in the brain, analogous to macrophages elsewhere in the body. Like macrophages, microglia are deeply involved in tissue maintenance as well as defense against pathogens and destruction of potentially cancerous, malfunctioning cells. Microglia adopt different packages of behaviors, called polarizations. In an aged tissue environment, microglia have a greater tendency to adopt an inflammatory polarization focused on defense rather than an anti-inflammatory polarization that aids in tissue maintenance. This shift towards maladaptive inflammatory signaling and immune behavior is characteristic of aging more generally. In the brain, microglia-driven inflammation harms tissue function, contributing to the onset and progress of neurodegenerative conditions.
Microglia, the resident innate immune cells of the central nervous system, are central players in brain development, healthy aging, and degenerative pathology, including Alzheimer's disease (AD). Aging is a major risk factor for AD, and various studies have identified alterations in microglial molecular signatures and morphological patterns that overlap with microglial states during aging. However, the mechanisms underlying the divergence of aging trajectories toward disease remain unclear. Thus, understanding the molecular changes in microglia during aging and AD pathology is crucial to elucidating the mechanisms that drive disease progression.
