Figure 1. Interaction between APOE genotype, Aβ deposition, and microglia.

The APOE ε4 allele is associated with greater β-amyloid (Aβ) deposition than APOE ε2 and ε3 alleles. Aβ parenchymal plaques attract microglia cells and cause their peri-plaque activation, which is proportional to Aβ plaque load across all APOE genotypes. Therapeutic anti-Aβ monoclonal antibodies (mAbs) bind deposited Aβ and activate microglia cells to clear Aβ through Fc receptor-mediated phagocytosis. The APOE ε4 allele is associated with greater microglia activation than APOE alleles ε2 and ε3 resulting in greater clearance of Aβ plaque load during Aβ-directed passive immunization.