One negatively correlated module M127 was enriched for genes related to functions and diseases involving dopamine synthesis and motor functions. This module also contained the PD variant-associated gene GCH1 (GTP cyclohydrolase 1) that is known to co-express with TH (tyrosine hydroxylase, the enzyme responsible for converting tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) in the dopamine synthesis pathway) to enhance dopamine production and enable recovery of motor function in rat models of PD34. In this study, both GCH1 and TH occur in M127 and thus were co-expressed across brain regions involved in Braak stages supporting their interaction. The higher expression in more vulnerable brain regions R1–R3 indicates that GCH1, TH, and possibly other genes within module M127 are essential to maintain dopamine synthesis that is affected in the early Braak stages of PD. Indeed, by inhibiting TH activity, α-synuclein can act as a negative regulator of dopamine release26,35. In this module, SLC18A2 (vesicular monoamine transporter 2) and SLC6A3 (dopamine transporter) were also present, which are important for dopamine storage and transport in the cell26. Interestingly, dopamine may increase neuronal vulnerability, as was suggested
