Studies have utilized humanized APOE mouse models crossed with amyloid and tau mouse models to show that, in addition to lipid trafficking, APOE functions in a variety of AD-relevant processes including amyloid clearance and tau-mediated neurodegeneration (Sullivan et al., 1997; Knouff et al., 1999; Huang et al., 2017; Liu et al., 2017; Shi et al., 2017; Huynh et al., 2019). This evidence concerns the gene APOE and Alzheimer disease.