Fig. 7: α-Synuclein proteoform levels in human putaminal synaptosomes.

A Group and Braak stage difference in total, pSer129, and CTT122 α-synuclein protein levels (over total protein) in putaminal synaptosomes. B Group and Braak stage difference in pSer129 and CTT122 fold change over total α-synuclein levels in iLBD and PD compared to control putaminal synaptosomes. Boxplots display the median (central line), the first and third quartiles (box hinges at the 25th and 75th percentiles), and whiskers that extend to minima and maxima. The statistical test used is a two-sided nonparametric rank-based estimation test with age and sex as covariates. Multiple testing comparison corrections were performed with the Tukey test. Exact p values: A tot α-syn (up): control vs PD p = 0.073, control vs iLBD p = 0.339; A tot α-syn (down): control vs Braak 1–6 all p > 0.05; pSer129 (up): control vs PD p = 0.043, control vs iLBD p = 0.392; pSer129 (down): control vs Braak 1–5 all p > 0.05, control vs Braak 6 p = 0.033; CTT122 (up): all p > 0.05; CTT122 (down): all p > 0.05; B pSer129 (up): control vs PD p = 0.137, control vs iLBD p = 0.179; pSer129 (down): control vs Braak 1–3 p = 0.817, control vs Braak 4 p = 0.095, control vs Braak 5 p = 0.090, control vs Braak 6 p = 0.035; CTT122 (up): control vs PD p = 0.178, control vs iLBD p = 0.530; CTT122 (down): control vs Braak 1–6 all p > 0.05. C, D Heatmap and scatterplot showing the correlation between pSer129 and CTT122 α-synuclein levels (over total protein) (C) and fold change over total α-synuclein levels in synaptosomes per case (labelled as in Supplementary Table 1) (D). The statistical test used is a two-sided Spearman’s correlation. Exact p values: C: rho = 0.88, p < 0.001; D: rho = 0.48, p = 0.004. The grey area around the regression line in C, D represents the standard error. The sample consists of n = 38 (control = 10, iLBD = 8, PD = 20), and three technical replicates are averaged for each brain donor. Source data are provided as a Source Data file. α-syn α-synuclein, n.a. not available (technical outliers), PTM post-translational modification, tot total. 0.10 < p ≤ 0.05#, p < 0.05*, p < 0.01**, p < 0.001***.