Complement and microglia mediate early synapse loss in Alzheimer mouse models

TLDR

The complement system and microglia normally clear cellular debris and excess synapses, but aberrant activation of this trash‑disposal mechanism may underlie Alzheimer’s disease pathology. The study shows that in adult mice prone to AD, complement binds synapses and microglial activity drives early synapse loss, which correlates with cognitive decline. Hong et al., Science, this issue p.

Abstract

Too much cleaning up The complement system and microglia seek out and destroy unwanted cellular debris for the peripheral immune system as well as excess synapses in the developing brain. Hong et al. now show how the system may go haywire in adults early in the progression toward Alzheimer's disease (AD). Aberrant synapse loss is an early feature of Alzheimer's and correlates with cognitive decline. In mice susceptible to AD, complement was associated with synapses, and microglial function was required for synapse loss. The authors speculate that aberrant activation of this “trash disposal” system underlies AD pathology. Science , this issue p. 712