The major histopathological hallmarks of AD are neurofibrillary tangles composed of hyperphosphorylated tau protein filaments, and extracellular senile plaques, which are deposits of β-amyloid (Aβ) generated via sequential proteolytic processing of the transmembrane amyloid precursor protein (APP) by two enzymes in the amyloidogenic processing pathway, namely β-secretase (β-site APP cleaving enzyme or BACE-1) and γ-secretase5, 6, 7. The gene discussed is APP; the disease is Alzheimer disease.