MAPT and Alzheimer disease: AD is neuropathologically characterized by extracellular amyloid plaques composed of β-amyloid peptides (Aβ) and intracellular neurofibrillary tangles constituted of hyperphosphorylated tau protein.3 Although the degree of tauopathy correlates strongly with cognitive decline in AD, the aggregation of Aβ has a critical role as early trigger, and recent longitudinal PET imaging studies indicated that cerebral Aβ deposition precedes the clinical symptoms of AD by a decade or more.4, 5