While APOE4's role in AD has often been attributed to its ability to increase the aggregation and decrease the clearance of Aβ (Rebeck et al., 1993; Schmechel et al., 1993; Ma et al., 1994; Castano et al., 1995; Bales et al., 1997; Holtzman et al., 2000; Castellano et al., 2011), APOE4 expression has also been shown to affect a wide array of Aβ-independent processes in the brain [see reviews by Huang (2010) and Wolf et al. (2013)], including a potential role in increasing the pathogenicity of other proteins, such as tau and α-synuclein (see review by Huynh et al., 2017). The gene discussed is MAPT; the disease is Alzheimer disease.