APP and its pathogenic cleavage product, β-amyloid, physically and functionally interact with ApoE receptors on multiple levels (Kounnas et al., 1995), by regulating the trafficking and processing of APP (Ulery et al., 2000; Pietrzik et al., 2002; Andersen et al., 2005; Hoe et al., 2005; Pietrzik and Jaeger, 2008; Marzolo and Bu, 2009), mediating amyloid clearance (Andersen et al., 2005; Deane et al., 2008) and by preventing amyloid-induced synaptic suppression at the synapse (Durakoglugil et al., 2009). The gene discussed is APP; the disease is amyloidosis.