Evolving insights into the identity and function of dark microglia

Microglia are the brain's primary innate immune cells, which maintain neural homeostasis through surveillance, debris clearance, and synaptic remodeling. Dark microglia represent a distinct state of microglia that came into recent focus due to their excessive physical contact with synapses in contexts of pathological synapse loss, predominantly in neurodegenerative conditions, such as Alzheimer's disease. Dark microglia are identified by their unique ultrastructural features, exhibiting a dark, condensed appearance under electron microscopy. They display signs of cellular stress and appear to be engaged in synaptic pruning. Here, we review recent advances in understanding these intriguing cells in the mammalian brain, from new molecular insights into their origin to their emerging functional roles across the lifespan, in both health and disease.