MAPT and Alzheimer disease: AD is characterized by progressive cognitive and behavioral impairment, and cerebral deposition of senile plaques (extracellular accumulation of beta-amyloid (Aβ) peptide) and neurofibrillary tangles (NFTs, intracellular accumulation of hyperphosphorylated tau protein) are unique neuropathological hallmarks of the disease (Hardy and Selkoe, 2002; Iqbal and Grundke-Iqbal, 2006).