Schematic illustration of tau isoforms, phosphorylation sites and mutations. Point mutations R5H, G272V, P301L, and R406W were created in the 2N4R (441) tau isoform. Arrows represent boundaries of K18 (amino acids 244–372) . N1 and N2 represent N-terminal exons 1 and 2. R1, R2, R3, and R4 represent microtubule binding domain repeats 1–4. Yellow circles designate 10 serine/threonine to glutamic acid mutations that occur in 352PHP tau . This mutant was created in the 352 tau isoform lacking N1, N2, and R2.