We propose that this “toxicity domain” contributes to Tau structural plasticity, as the occupation state of Ser238, Thr245, and Ser262 affects the phosphorylation state of additional proximal sites such as Ser202/Thr205 (AT8), Thr212/Ser214 (AT100), but also the distant Ser396 at the far carboxy-terminus of the protein (Figure 4), which when phosphorylated is also enriched in the CSF from AD patients (Russell et al., 2017). This evidence concerns the gene MAPT and Alzheimer disease.