Last reviewed: June 1, 2026
2016Nature
Schizophrenia risk from complex variation of complement component 4
Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, et al.
Abstract summary
Demonstrated that elevated C4A expression from specific structural genomic variants drives excess synaptic pruning through C3 deposition and microglial complement receptor-mediated elimination. Identified a mechanism linking complement-mediated synaptic pruning to schizophrenia risk. Microglia are the effector cells mediating complement-dependent synapse elimination.
Evidence labels
human geneticsanimal model
Targets
Diseases
- Brain aging
Species
human, mouse
Methods
genome-wide association study, mouse genetics, immunohistochemistry
Therapeutic relevance
Established complement-mediated synaptic pruning as a druggable mechanism with relevance beyond Alzheimer's disease to psychiatric disorders.
Last reviewed: June 1, 2026