C3
Complement component 3
Also known as: C3, complement C3
Biology & Mechanism
C3 is the central effector of the complement cascade and a key mediator of synapse elimination by microglia. C3b opsonizes synapses and neurites for phagocytosis by microglia via the complement receptor CR3 (ITGAM/CD11b). Elevated C3 expression in the aging and Alzheimer's disease brain contributes to excessive synaptic pruning and neurodegeneration. C3 is produced by both astrocytes and microglia in the diseased brain.
Open Questions
- —Does complement-mediated synapse elimination serve a protective or harmful role in early versus late Alzheimer's disease?
- —Can selective inhibition of the C3-CR3 axis in the CNS prevent synapse loss without impairing phagocytic clearance of amyloid?
- —What are the upstream triggers of C3 upregulation in the aging brain?
Sources
- C3 and C3aR mediate different aspects of emotional memory (2020)
Last reviewed: June 1, 2026