Evidence from animal models of Alzheimer’s disease has implicated complement as a trigger for and driver of synaptic loss, an early and critical event in neurodegeneration that strongly correlates with cognitive decline; indeed, mice deficient in C1q, C4 or C3 all show defects in developmental synaptic pruning leading to accumulation of supernumerary synapses [51]. Here, C4A is linked to early-onset autosomal dominant Alzheimer disease.