APP and Alzheimer disease: Pathogenic variants in the amyloid precursor protein (APP), presenilin 1 (PSEN1) or presenilin 2 (PSEN2) genes cause an early onset AD phenotype, usually with conventional AD proteinopathy of aggregated amyloid beta (Aβ) and hyperphosphorylated tau (P-tau) in deposits of neuritic plaques and neurofibrillary tangles [2].