MAPT and Alzheimer disease: Neuropathologically, AD is defined by neurodegeneration with the presence of extracellular senile plaques consisting of β amyloid (Aβ) and intraneuronal neurofibrillary tangles consisting of aggregated tau (Grundke-Iqbal et al., 1986; Ingelsson et al., 2004), which first appear in the hippocampus and then spread as the disease progresses.