Furthermore, pathological analyses of post-mortem brain tissue from individuals with AD have revealed heightened intra-neuronal accumulation of Aβ in ApoE4 carriers (Christensen et al., 2010), plaque deposition in the brain parenchyma (Polvikoski et al., 1995; Schmechel et al., 1993; Tiraboschi et al., 2004), formation of neurotoxic Aβ oligomers (Koffie et al., 2012), and extensive cerebral amyloid angiopathy (CAA) (Rannikmäe et al., 2014; Shinohara et al., 2016). Here, APOE is linked to Alzheimer disease.