Synapse elimination by complement deposition and microglial engulfment in early Alzheimer's disease

Abstract summary

Demonstrated that microglia engulf synaptic material through a CR3/C3-dependent mechanism during normal postnatal development. Using two-photon microscopy and immunoEM, showed microglia internalize presynaptic terminals tagged with C3 and C1q. In retinogeniculate refinement, C3 knockout mice have impaired synapse elimination, establishing complement-CR3 as the core synaptic pruning mechanism.

Evidence labels

Therapeutic relevance

Established the mechanistic basis for complement-CR3 as the synaptic pruning pathway, directly targeted by anti-complement therapies in clinical development.