MAPT and Alzheimer disease: Histopathologically, AD is characterized by two pathognomonic hallmarks (Figure 1) [6]: (1) the intracellular deposition of abnormally phosphorylated Tau protein that promotes the formation of neurofibrillary tangles (NFTs) in the cerebral cortex and subcortical gray matter (Figure 1a); and (2) extracellular aggregates of Amyloid-beta peptide (Aβ) fibrils in the form of neuritic plaques (NPs; Figure 1b).