APP and familial Alzheimer disease: A fully penetrant autosomal dominant inheritance of amyloid precursor protein (APP), presenilin-1 (PS1), or presenilin-2 (PS2) mutations drives the development of the disease in a small fraction of patients [0.5–1%; familial AD (fAD)], however for the remaining 99% classified as sporadic AD (sAD), the etiopathogenesis remains unresolved (Reitz et al., 2020).