,26,27,28 Previous studies have demonstrated that enhanced C3/C3aR signaling promotes synaptic loss in models of Alzheimer’s disease and multiple sclerosis,18 whereas C3 deficiency confers neuroprotection against cognitive decline,29 and hippocampal CA3 synapse and neuron loss.28 This evidence concerns the gene C3AR1 and early-onset autosomal dominant Alzheimer disease.