For instance, AD brains exhibit increased levels of the carboxyl terminus of Hsp70-interacting protein (CHIP or STUB1) (Sahara et al., 2005), the E3 ubiquitin ligase that ubiquitinates tau paired helical filaments, targeting it to the 26S proteasome (Mori et al., 1987; Petrucelli et al., 2004). This evidence concerns the gene MAPT and Alzheimer disease.