Spatial Transcriptomics Analysis of Neuroinflammatory Pathways Associated with Parkinson’s Disease Genes

This study explores the spatial organization of Parkinson’s disease (PD)-related genes and neuroinflammatory markers in the brain using high-resolution MERFISH spatial transcriptomic data. We focused on spatial relationships among core cell types—dopaminergic, astrocytic, vascular, and immune—and their associations with cells expressing high levels of PD and inflammation-related genes. Neighborhood enrichment and density correlation analyses revealed strong co-localization of astrocytes and vascular cells, while dopaminergic and immune cells were spatially segregated. Spatial expression maps showed regionally restricted gene activity, and combined analysis of cell types and gene-high expressing cells highlighted spatially structured neighborhoods. Clustering of gene-high groups across three brains yielded reproducible gene modules enriched in immune response and neurotransmitter regulation pathways. These findings reveal consistent spatial interactions and transcriptional modules that may underlie PD-related neuroinflammation, offering insights into disease-associated tissue architecture.