Fig. 1

Peptide selection for antibody generation. A schematic representation of all six tau isoforms expressed in human adult brain is shown. The two hexapeptide sequences necessary to initiate tau aggregation, PHF6* and PHF6, are also indicated. To generate potential therapeutic antibodies, two peptide immunogens contained within the microtubule-binding region (MTBR) of 4R tau isoforms were selected. Peptide 1 (273–291) contained two amino acids within the R1 region with the remainder in R2 encompassing the PHF6* motif. Peptide 2 (296–314) contained ten amino acids within R2 and nine in R3, also including the PHF6 motif as well as the P301 residue (bold and underlined), often introduced as mutated in pre-clinical research models. Amino-acid numbering according to largest (2N4R) isoform (NP_005901)