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 Aβ-accumulation because ApoE does not bind Aβ as a native lipoprotein (Verghese et al., 2013). ApoE4 enhances Aβ-oligomerization, suggesting that ApoE4 could predispose to AD by increasing toxic Aβ oligomers (Hashimoto et al., 2012). Mice express only a single ApoE allele; exchanging endogenous ApoE in mice with human ApoE2, ApoE3, and ApoE4 produces complex effects that include changes in Aβ aggregation and clearance (Castellano et al., 2011; Fryer et al., 2005).
