Fig. 1

Major tau domains and phosphorylation sites. The amino acid sequence of the longest isoform of tau protein (2N4R, 1–441aa) in the central nervous system can be roughly divided into the projection domain on the N-terminal and the microtubule assembly domain on the C-terminal half of the protein. Tau can have up to two inserts in the N-terminal (here shown as N1, N2) and three or four repeats on the C-terminal (R1, R2, R3, R4). These combinations lead to a total of six different isoforms in the central nervous system. The VQIVYK sequence in R2 and VQIINK sequence in R3 are important for aggregation of tau. Several important phosphorylation sites that are associated with tau pathology are shown (p202/205, p212/214, p231, p396/404). These sites are targets for widely used antibodies such as AT8 or PHF1. Several C-terminal truncations have been identified that promote aggregation. Two wellcharacterized truncations are shown here (Δ391 and Δ421)