MAPT and Alzheimer disease: Similarly, pathological hallmarks of AD, including the extracellular aggregation of amyloid β (Aβ) into amyloid plaques and the intracellular accumulation of the tau protein into neurofibrillary tangles (NFTs), begin decades before cognitive decline and clinical diagnosis (Hardy and Selkoe, 2002; Bateman et al., 2012; Musiek and Holtzman, 2015).