MAPT and Alzheimer disease: These observations suggested that Aβ may be both necessary and sufficient for pathogenesis and led directly to the establishment of the amyloid hypothesis, which proposes that extracellular deposits of Aβ, particularly the longer and more aggregation-prone Aβ1–42 isoform, trigger a chain of events that includes the recruitment and hyperphosphorylation of tau, and leads to the loss of synapses and eventually neurons themselves that characterise AD [6].