MAPT and Alzheimer disease: Hyperphosphorylated tau is ubiquitinated in patients with AD (Mori et al., 1987; Perry et al., 1987; Cripps et al., 2006) and interestingly, dysfunction of either the proteasomal or lysosomal degradation pathways may lead to accumulation of excessive ubiquitinated tau species in AD patients that can contribute to NFT formation in disease (Wang and Mandelkow, 2012; Cook et al., 2014b).