MAPT and Alzheimer disease: From a neuropathological perspective, AD is characterized by the accumulation of extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles of phosphorylated tau protein (p-tau) in the brain, which initiates a neurotoxic cascade of progressive neuronal and synaptic loss in the hippocampus and surrounding medial temporal lobe (Bloom, 2014), and general brain atrophy (Pini et al., 2016).