Animal models carrying mutations in the APP, in combination with human ApoE isoforms, confirm that the presence of the ApoE ε4 allele significantly enhances Aβ accumulation, largely through impaired clearance mechanisms, further substantiating the genetic interplay between mood disorders and AD pathophysiology (Bales et al., 2009; Castellano et al., 2011). Here, APOE is linked to Alzheimer disease.