Objective: To determine whether transcriptomic and proteomic changes predict better motor outcomes after deep brain stimulation (DBS) surgery in Parkinson’s disease (PD).

Background: DBS is a well-established surgical therapy used to alleviate specific motor symptoms of PD.  However, the mechanism of action of DBS remains unclear.  Transcriptomics and proteomics data integrated with clinical information can provide insights about disease progression and treatment response.

Method: We screened 16K genes and 5K proteins in whole blood and CSF from PD individuals with (n = 42) and without DBS (n = 527) from the Parkinson’s Progression Markers Initiative (PPMI) cohort. We applied differential expression analysis using limma and adjusted for age at baseline, sex, and levodopa equivalent daily dose, with the first four proteomic principal components (PCs) for CSF proteins. We also performed a KEGG pathway analysis and mined single-cell transcriptomic data to map the cell-specific expressions.

Results: We have identified 42 PD participants (six GBA carriers, 12 LRRK2 carriers, and 23 sporadic cases) in the PPMI dataset who had DBS surgery and have transcriptomics data from whole blood and proteomics data from CSF.  This cohort has a mean age of 56.8 ± 8.2 years at study enrollment, ~2.2 male to female ratio, a mean of 1.82 ± 2.07 years from symptom onset to PD diagnosis, and had DBS implanted on average 92 ± 30.2 months after diagnosis. We found 83 downregulated genes (autophagy) enriched in microglia and endothelial cells and 239 upregulated genes (calcium signaling and axon guidance) enriched in neurons and astrocytes.  We also found 60 downregulated proteins (PI3K-Akt signaling pathway) enriched in microglia and 104 upregulated proteins (cytokine-cytokine receptor interaction, Ras, Rap1, PI3K-Akt, and MAPK signaling pathway) enriched in neurons of PD patients with DBS.

Conclusion: Transcriptomics and proteomics are novel techniques used to identify biomarkers of effective DBS in PD.

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/transcriptomic-and-proteomic-profiling-for-effective-deep-brain-stimulation-in-parkinsons-disease/