Figure 1.

PTM-mediated tau toxicity. Tau isoforms contain up to two N-terminal domains and either 3 or 4 “R domains” (2N4R tau shown, though sporadic AD involves both 3R and 4R tau). The proline-rich domain (PRD) is just upstream of the MTBDs and commonly contains PTMs. The abundance of these PTMs increases stoichiometrically as AD progresses and generates toxic tau species which are likely involved in neurodegeneration. The PTM panel above was inspired by Wesseling et al. [24].