Fig. 1

A schematic showing mutations of MAPT and composition of tau isoforms. The H1 and H2 haplotypes are formed by the 900 kb inversion in the q21.3 region of chromosome 17. The H1 haplotype is often the one contributing to disease initiation due to multiple missense mutations from exon 1 to 13, especially on exon 10. The tau protein can be classified into 6 isoforms depending on the number of amino inserts (0N, 1N, 2N) on exons 2 and 3 and the number of microtubule-binding domains (3R, 4R). Exon 10 encodes the R2 domain, and its alternative splicing produces 3R or 4R tau isoforms. The microtubule-binding domain contains hexapeptide motifs VQIINK in R2 and VQIVYK in R3. Interactions between the two motifs promote dimer formation of tau [1, 2, 73]