Detailed molecular characterization of cell-specific transcriptomic states throughout multiple brain regions beyond nigrostriatal dopaminergic degeneration will provide mechanistic insights into motor and non-motor PD symptoms. We will integrate neuropathology and snRNA-Seq data to identify a divergent molecular signature and/or shared aberrant pathways in various affected brain regions in PD. We will incorporate snRNA-Seq data, and GWAS hits from PD and Dementia with Lewy Bodies (DLB) to identify cell-type-specific expression and quantitative trait loci and to determine the genes involved in genetically enriched causal pathways. We will also use the expression signatures from snRNA-seq to prioritize causal genes under multi-gene genome-wide loci. We expect to uncover cell-type-specific differentially expressed genes (DEGs) in unexplored but affected brain regions in PD that will provide the foundation for understanding novel cellular and molecular mechanisms in PD.
