APOE and Alzheimer disease: In AD model mice overexpressing human mutant APP, the knockout of endogenous ApoE leads to a significant reduction in Aβ deposition in the brain, along with lowered Aβ40 and Aβ42 deposits, underscoring the substantial role of ApoE in Aβ fibril formation and amyloid deposition (Holtzman et al., 2000; Bales et al., 1999; Bales et al., 1997).