APP and Alzheimer disease: (a) Mendelian or mutational defects in genes are directly linked to AD, including (i) >30 mutations in the amyloid beta (Aβ) precursor protein (APP) gene (21q21) (AD1), (ii) >160 mutations in the presenilin 1 (PSEN1) gene (14q24.3) (AD3), and (iii) >10 mutations in the presenilin 2 (PSEN2) gene (1q31–q42) (AD4) [9, 24, 25].