MAPT and Alzheimer disease: The prevailing theory regarding the cause of AD is the amyloid cascade hypothesis, which posits that overproduction of Aβ from amyloid precursor protein (APP) initiates a series of events, including synaptic dysfunction, microglial and astrocytic activation and hyperphosphorylation of tau, which culminates in widespread neuronal death and neurodegeneration (Hardy and Selkoe, 2002).