We further explored the relationship between SNCA expression and PD vulnerability in more detail. SNCA was positively correlated with Braak stages in non-neurological brains from the AHBA, with a lower expression in regions R1–R2 and higher expression in R3–R6 (Fig. 5a–c), which was replicated in larger cohorts of non-neurological individuals (Fig. 5d, e). This observation suggests that lower SNCA expression indicates high vulnerability of brain regions to develop LB pathology. We further validated this concept in two cohorts of PD patients in which SNCA expression similarly increased across the medulla oblongata (R1), locus coeruleus (R2), and substantia nigra (R3) of PD and iLBD patients, and age-matched controls. SNCA was significantly lower expressed in region R1 compared to R2 and R3 in PD and iLBD patients, but not in controls (BH-corrected P < 0.05, t-test; Fig. 5f). In the PD RNA-seq dataset, SNCA was significantly lower expressed in the substantia nigra (R3) compared to the medial temporal gyrus (R4/R5) in PD patients, but again not in controls (BH-corrected P < 0.05, DESeq2; Fig. 5g). Altogether, SNCA expression patterns could be replicated
