Reflecting the prevailing dogma that AD has a central aetiology, studies investigating potential mechanisms underpinning association of APOE4 genotype Alzheimer’s risk have focussed on effects on amyloid precursor processing, potential effects on oligomerisation and degradation, on synaptic plasticity, tau phosphorylation, neuroinflammation and modulating TREM-2 mediated microglial phagocytosis (42). The gene discussed is APOE; the disease is Alzheimer disease.