Fig. 5

aSyn proteoforms show differential distribution over detergent-soluble and -insoluble fractions. Levels of pSer129, 119CTT and 122CTT aSyn proteoforms expressed as % of putative ‘total’ aSyn levels (see main text) in detectable detergent-soluble (A) and -insoluble (B) brain fractions included in this study. C Distribution of different aSyn proteoforms over sequential fractions, presented as an ‘insolubility’ index by the ratio of protein levels in detergent-insoluble over detergent-soluble fractions of the same tissue specimen. Note: samples were only included in this analysis when all proteoforms were detectable in detergent-soluble/insoluble fractions. Consequently, A includes data from patients of all diagnostic groups in our cohort as well as NNS, while B and C only include data from selected patients with synucleinopathies, as levels of aSyn proteoforms was undetectable in detergent-insoluble fractions of all donors without synucleinopathy and in remaining donors with synucleinopathy. Statistical comparison between different aSyn proteoforms was done using non-parametric Friedman tests and pairwise comparisons using Dunn’s post-hoc tests. *p < 0.05; **p < 0.01; ***p < 0.001, ****p < 0.0001. Bar graphs in A and B indicate mean ± standard deviation, bar graphs in C indicates mean ± 95% confidence interval