The ε-4 allele of the apolipoprotein E (APOE) is a risk factor in the pathogenesis of late-onset of AD, playing an important role in amyloid β (Aβ) brain metabolism (APOE ε-4 exacerbates deposition of Aβ in the brain and tau-mediated neurodegeneration) [40,41,42]. Here, APOE is linked to Alzheimer disease.