The Exon-Based Transcriptomic Analysis of Parkinson's Disease.

Area of Science:

• Neuroscience
• Genomics
• Biomarker Discovery

Background:

• Parkinson's disease (PD) presents complex pathophysiology and diagnostic challenges.
• Early-stage PD shows minimal differences in exon expression between patients and controls.
• Identifying reliable biomarkers is crucial for understanding and managing PD.

Purpose of the Study:

• To investigate changes in exon expression in Parkinson's disease patients over time.
• To identify potential RNA-based biomarkers for PD diagnosis and progression monitoring.
• To correlate gene expression changes with known PD pathophysiology.

Main Methods:

• Longitudinal whole transcriptome analysis of blood samples from the Parkinson's Progression Markers Initiative (PPMI) cohort.
• Focus on differential exon expression analysis between PD patients and healthy controls.
• Comparison of exon expression changes over a three-year period.

Main Results:

• No significant exon expression differences were observed at the time of PD diagnosis.
• Twenty-seven exons were differentially expressed in PD patients three years post-diagnosis compared to controls.
• Thirteen exons showed differential expression during the three-year progression of PD, with minimal changes in controls attributed to aging.
• Differentially expressed exons were associated with innate immune response and lysosomal activity.
• A decline in OPN1MW3 gene expression, related to color vision, was observed in PD patients.

Conclusions:

• Exon expression patterns evolve over time in Parkinson's disease, offering potential biomarkers.
• Immune response and lysosomal activity pathways are implicated in PD pathophysiology.
• The observed decline in OPN1MW3 suggests color vision changes may serve as a practical biomarker for monitoring PD progression.