Fig. 7: Tau post-translational modification (PTM) events.

PTMs are numbered according to full-length (2N4R) tau protein. Each box represents a different condition. The line inside the box denotes the median value (50th percentile), while the box contains the 25th to 75th percentiles of dataset. The whiskers mark the 5th and 95th percentiles, and values beyond these upper and lower bounds are considered outliers. PTMs are either observed alone or as PTM events, i.e., associated with other, nearby PTMs. The comparison between insoluble (left) and soluble (right) tau PTM events indicates that the combination of PTMs is more frequently observed in soluble than in insoluble tau, suggesting a protective effect of these additional PTMs against tau aggregation. Non-detected modified peptides were set arbitrarily to 0. The detection of the same peptide differently modified ensures that the absence of detection was not due to lack of ionisation or other methodological reasons. Data were analysed using an unpaired Wilcoxon test (*P < 0.05, **P < 0.005, ***P < 0.0005). All statistical tests were two-tailed. S serine, T threonine; K lysine; Ub- ubiquitination; P- phosphorylation. AD Alzheimer’s disease (n = 15 biologically independent samples); CBD corticobasal degeneration (n = 5 biologically independent samples); PiD Pick’s disease (n = 5 biologically independent samples); FTLD frontotemporal lobe degeneration (n = 10 biologically independent samples, including FTLD-4R, n = 4 and FTLD-3R, n = 6); control individuals, CTL (n = 5 biologically independent samples). Source data are provided as a Source Data file (see sheet 3 for the abundances values and sheet 5 for the Wilcoxon test’s exact p values).