MAPT and Alzheimer disease: Alzheimer’s disease is pathologically defined by senile gray matter plaques consisting of neurotoxic deposits of extracellular amyloid–beta (Aβ) 42 protein, intracellular neurofibrillary tangles (NFTs) including the three repeat (3R) and four repeat (4R) tau isoforms, and decreased neuronal density from neuronal death.