Complement and microglia mediate early synapse loss in Alzheimer mouse models

• DOI: 10.1126/science.aad8373
• Publication Date: 2016-04-01T03:45:32Z
• Authors: Soyon Hong; Victoria F. Beja-...; Bianca M. Nfonoyim; Arnaud Frouin; Shaomin Li; Saranya Ramakrishnan; Katherine M. Merry; Qiaoqiao Shi; Arnon Rosenthal; Ben A. Barres; Cynthia A. Lemere; Dennis J. Selkoe; Beth Stevens
• Keywords: Mice, Knockout; Amyloid beta-Peptides; Complement C1q; Long-Term Potentiation; Synaptophysin; Macrophage-1 Antigen; Membrane Proteins; Plaque, Amyloid; 3. Good health; Disease Models, Animal; Mice; Phagocytosis; Alzheimer Disease; Synapses; Animals; Complement Pathway, Classical; Microglia; Cognition Disorders; CA1 Region, Hippocampal; Disks Large Homolog 4 Protein; Guanylate Kinases

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