The identity and function of dark microglia

Dark microglia are an ultrastructurally distinct subset of microglia. They are consistently observed across species in pathological conditions, particularly Alzheimer’s disease, and exhibit a mixed presence in inflammatory paradigms. 

Based on their disease-driven emergence, proximity to plaques, molecular markers, and dependency on the TREM2 receptor, dark microglia are speculated to be a subset of disease associated microglia (DAM).

The purported synapse-pruning role of dark microglia aligns closely with that of a DAM subset exhibiting an integrated stress response (ISR).

While dark microglia are largely ISR+, additional molecular markers are needed to expand the study of these cells beyond the scope of electron microscopy.

Outside of disease, dark microglia appear in early development, coinciding with periods of heightened microglial synaptic pruning.

https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(25)00240-1

https://sciencemission.com/identity-and-function-of-dark-microglia