MAPT and Alzheimer disease: This sequence of findings became formative work toward the neuron-centric amyloid hypothesis of AD, whereby accumulation of Aß peptide aggregates in the brain is postulated to drive other AD pathologies, including neurofibrillary tangles of hyperphosphorylated tau (p-tau) protein inside of neurons and, ultimately, neurodegeneration (Hardy & Higgins, 1992; Hardy & Selkoe, 2002).