Human ApoE is expressed in three genetic isoforms, ApoE2, ApoE3, and ApoE4, that encode proteins which differ only in two residues. Strikingly, the ApoE4 allele is the most important genetic risk factor for Alzheimer’s disease (AD), whereas the ApoE2 allele is protective (Strittmatter et al., 1993). How ApoE isoforms predispose to AD, or protect against it, is incompletely understood (Holtzman et al., 2012; Kanekiyo et al., 2014). A central feature of AD pathology is formation of amyloid-β (Aβ) oligomers and plaques (Pimplikar et al., 2010; De Strooper and Karran, 2016; Goedert, 2015). Although the precise role of Aβ in AD remains debated, Aβ clearly constitutes a central component of AD pathogenesis that correlates with neuronal cell death and that may perform a causative role in AD pathogenesis (Goedert, 2015; De Strooper and Karran, 2016). Both in AD patients and in cognitively apparently normal people, ApoE4 is associated with increased Aβ-accumulation in brain (Schmechel et al., 1993; Fouquet et al., 2014). ApoE binds Aβ in its delipidated form, but this binding is probably not responsible for the effect of ApoE4 on
