A voxel-level degree centrality study in Parkinson's disease and the correlation with transcriptomes

Area of Science:

• Neuroscience
• Genomics
• Systems Biology

Background:

• Altered brain network connectivity, measured by degree centrality, is associated with Parkinson's disease (PD) symptoms.
• The relationship between regional degree centrality differences in PD patients and spatial gene expression patterns is not well understood.
• Underlying biological pathways and cell types contributing to these changes require clarification.

Purpose of the Study:

• To compare regional degree centrality between PD patients and healthy controls.
• To investigate associations between degree centrality alterations and brain-wide gene expression.
• To identify enriched pathways and specific cell types involved in PD-related connectivity changes.

Main Methods:

• Voxel-wise degree centrality maps were generated and compared between PD patients and controls using t-tests.
• Partial least squares (PLS) regression integrated degree centrality data with gene expression from the Allen Human Brain Atlas.
• Enrichment analyses (Metascape) and cell-type specificity assessments identified key biological pathways and cellular contributors.

Main Results:

• Significant degree centrality alterations were observed in PD patients compared to controls.
• These connectivity changes spatially correlated with a gene expression pattern identified by PLS component 2.
• Associated genes showed predominant expression in astrocytes and neurons, involved in synapse organization.

Conclusions:

• This research connects functional brain network disruptions in PD to specific transcriptomic signatures.
• Astrocytes and neurons are identified as critical cell types contributing to these PD-related changes.
• Findings provide insights into the cellular and molecular basis of brain connectivity alterations in Parkinson's disease.