Fig. 1: Profiling the aggregation propensity of the tau repeat domain.

a Sequence of tau (top) and sliding window approach (15-residue windows incorporating 3-residue increments) used to generate a peptide library spanning the tau repeat domain. b Aggregation score profile of the tau repeat domain, as predicted by CORDAX (purple line) and WALTZ (cyan area). The five regions predicted in total, including PAM4 and the previously identified PHF6* and PHF6, are highlighted in colour-shaded boxes. c, d End-state fluorescence analysis using Th-T (top) and pFTAA (bottom). Peptides showing increased fluorescence compared to the vehicle control (shown as a black bar) were identified as positive for aggregation. Windows containing each one of the predicted APRs are shown in colour-shaded areas as in b. Bar plots indicate mean values +/− SD (n = 3 biologically independent samples). Statistical significance was determined using one-way ANOVA with Tukey’s test for multiple comparisons. e Electron micrographs validating the formation of amyloid-like fibril aggregates by the identified peptide windows. Colour-coded outlines matching the shaded areas shown in b–d are used to highlight the corresponding predicted APRs contained in each peptide window. Underlined segments represent the sequences predicted in b. A single representative image is shown (n = 3 independent repeats).