Tau misfolding and aggregation into highly ordered β-sheet-rich paired helical filaments (PHFs) that subsequently deposit in the form of neurofibrillary tangles (NFTs) (Figure 1b) are implicated in a heterogeneous group of aging-related neurodegenerative disorders referred to as tauopathies, which include Alzheimer’s disease (AD), Pick’s disease (PiD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP) (Table 1) [15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.