β-Amyloid precursor protein, presenilin and tau are undoubtedly pivotal to understanding the pathogenesis of AD and there are as yet no convincing refutations of the classical amyloid cascade hypothesis of AD, which postulates that, Aβ over-production leads to the pathogenic hyper-phosphorylation of tau resulting in the formation of neurofibrillary tangles (NFTs) and neurodegeneration. The gene discussed is MAPT; the disease is Alzheimer disease.