SNCA expression in Braak stage-related regions R1–R6 of non-neurological individuals and Parkinson’s disease (PD) patients.a Boxplots of SNCA expression in regions R1–R6 (colored) for each donor (opacity) in the AHBA (number of samples in Supplementary Table 1). Meta-analysis of b SNCA correlation with Braak stages and c SNCA expression fold-change (FC) between region R1 and R6 across the six donors in the AHBA. To calculate the summary effect size (orange diamonds) from the individual effect sizes (turquoise squares), the 95% confidence intervals (CI) and weights are taken into account. The positive correlation with Braak stages was validated in datasets from two healthy cohorts, d UK Brain Expression Consortium (UKBEC; 134 donors) and e Genotype-Tissue Expression Consortium (GTEx; 88-129 donors), and f, g two PD cohorts with PD patients, incidental Lewy body disease (iLBD) patients, and non-demented age-matched controls (number of samples in Supplementary Tables 2 and 3). In the PD datasets, SNCA expression was tested for differential expression between regions and conditions (red, BH-corrected P < 0.05, t-test and DESeq2, respectively). The boxplots indicate the median and interquartile range (25th and 75th percentiles) with whiskers indicating 1.5 times the interquartile range; outliers beyond the whiskers are plotted individually. h SNCA was still significantly differentially expressed between region R1 (black) and R6 (red) when correcting for five main cell-types with PSEA in the AHBA (BH-corrected P < 0.05, t-test). Significant BH-corrected P-values are highlighted in red together with cell-type specific fold-changes (slope change of red line). PSEA results for PD data are shown in Supplementary Fig. 13.
