Disease-associated microglia in neurodegenerative diseases: Friend or foe?

Recent advances in single-cell transcriptomics have led to the identification of disease-associated microglia (DAM) as a distinct, conserved microglia state associated with mouse models of Alzheimer's disease (AD) and amyotrophic lateral sclerosis, and with aging. DAM are characterized by downregulation of homeostatic genes and upregulation of lipid metabolism and phagocytosis genes, including key risk factors for AD in humans. Although characterized in models of AD, whether DAM acts as universal sensor across all neurodegenerative diseases remains unknown. This Essay discusses the dynamics, origins, and therapeutic potential of DAM in neurodegeneration, alongside evidence supporting a protective role for them in regulating disease processes.