MAPT and Alzheimer disease: In a physiological context, tau remains soluble and functional, but in the case of idiopathic neurodegenerative disorders such as sporadic Alzheimer’s disease (AD), elevated levels of tau (Khatoon et al., 1992) become highly susceptible to conformational changes, aggregation, and oligomerization and further assembly into paired helical filaments (PHFs), which then nucleate into neurofibrillary tangles (NFTs; Wille et al., 1992; Crowther et al., 1994; Wilson and Binder, 1995; Patterson et al., 2011).