Figure 1.

Post-translational modifications are found throughout tau and associate with all tauopathies. (A) Schematic representation of the structural features of 2N4R tau protein. Tau exists in 6 isoforms generated by the alternative splicing of exons 2, 3, and 10 of the MAPT gene. The isoforms include 0, 1, or 2 amino-terminal inserts (blue rectangles) and three (3R) or four (4R) microtubule-binding potential repeat domains (green rectangles). (B) Pathological and genetic classification of tauopathies as they relate to post-translational modifications (PTMs). Primary tauopathies fall under the umbrella pathological term frontotemporal lobar degeneration with tau inclusions (FTLD-Tau) and include Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia with parkinsonism (FTDP-17). Alzheimer's disease, a secondary or mixed tauopathy, is characterized by the presence of extracellular inclusions containing Amyloid β (Aβ) protein. Tauopathies are also classified depending on tau isoform composing the intracellular inclusions. PiD is a 3R-predominat tauopathy, PSP, and CBD are 4R tauopathies and FTDP-17 and AD are 3R:4R tauopathies. The PTMs observed in tau, the targeted residues and the disease where they have been observed is also shown.