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 by an earlier study showing that α-synuclein is selectively toxic in dopaminergic neurons, and neuroprotective in non-dopaminergic cortical neurons36. Cell-type marker enrichment showed that module M127 was enriched for microglia- and neuronal markers, suggesting a role in neuroinflammation. α-Synuclein aggregates evoke microglia activation which in turn promotes aggregated protein propagation to other brain regions, possibly even from the gut or periphery to the brain27,33. The higher expression of microglial genes within module M127 may contribute to the higher vulnerability of brain regions affected during preclinical stages to form protein aggregates. Further investigation of genes within module M127 will provide a better understanding of the molecular mechanisms underlying microglia activation, dopaminergic pathways and motor functions.
