There are several excellent reviews that have discussed the mechanisms and relationships of UPS and tau phosphorylation in AD development (Ciechanover and Kwon, 2015; Gentier and van Leeuwen, 2015; Kumar et al., 2015), and also many reviews that highlight deubiquitination enzymes and the E3 ligases in the role of substrate recognition and ubiquitination. This evidence concerns the gene MAPT and Alzheimer disease.