Mass spectrometric analysis of soluble PHF-tau immunopurified from AD brains revealed three putative ubiquitylated lysine residues: K254 and K353 located in the R1 and R4 repeat sequences, respectively, and K311 found in the flanking region between the R2 and R3 repeat sequences (Figure 3C; Cripps et al., 2006). Here, MAPT is linked to Alzheimer disease.