TREM2 and neurodegenerative disease: Eliminating microglia or attenuating microglial activation in neurodegenerative diseases restored spine number and synaptic integrity and improved functional outcomes.92 In AD brains, microglia mediate aberrant synapse loss via complement mediators (especially C1q and C3),93,94 as well as through the triggering receptor expressed on myeloid cells 2 (TREM2) signaling.95 Additionally, microglia phagocytosis of synapses is also affected by astrocytes.