MAPT and Alzheimer disease: Nevertheless, over the last three decades, the “amyloid cascade hypothesis” has been proposed and amended as a potentially unifying theory of AD, with the premise that Aβ accumulation represents the initiating toxic event triggering a neurodegenerative cascade that involves amyloid deposition, followed by Tau hyperphosphorylation, inflammation, oxidative stress, synaptic and neuronal loss2–5.