Fig. 7

Schematic summary of results and hypothesis: In Alzheimer’s disease (AD) mouse models with profound neuron loss (e.g. 5XFAD), GPNMB-positive activated microglia cells cluster around individual amyloid plaque cores. In contrast, microglia cells are persistently GPNMB-negative in healthy wild-type mice or AD models showing abundant plaque pathology without neuron loss. Under neurodegenerative conditions, microglia switch from a homeostatic to a disease-associated phenotype, which has been called “microglial neurodegenerative phenotype” (MGnD) or “disease-associated microglia” (DAMs), and which is characterized by the upregulation of a subset of genes including GPNMB. The precise role of GPNMB in the central nervous system is not yet known, however, evidence indicates that it has anti-inflammatory and regenerative functions. Individual components of the scheme have been taken from: http://smart.servier.com