Although the exact mechanism underlying AD pathogenesis is being investigated, two major neuropathological hallmarks of AD are senile plaques, which are formed by extracellular accumulation of amyloid β (Aβ40/42) fibrils, and intracellular neurofibrillary tangles (NFT) which contain aberrantly hyperphosphorylated tau as paired helical filaments (PHFs). The gene discussed is MAPT; the disease is Alzheimer disease.