In addition to the C3/CR3 pathway, C3 secreted by A1 astrocytes interacts with microglia C3aR to regulate microglia phagocytosis, β-amyloid, and neuroinflammation in AD models, thereby worsening cognitive function by impairing dendritic cell morphology and synaptic function (Lian et al., 2016; Litvinchuk et al., 2018; Liu et al., 2020). This evidence concerns the gene CRIPTO3 and Alzheimer disease.