CNS*2026 Halifax

Introduction
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and heterogeneous clinical trajectories with motor and non-motor symptoms [1]. Predicting disease progression requires biomarkers capturing both brain alterations and underlying molecular mechanisms. Neuroimaging reveals structural brain changes [2], while transcriptomic and proteomic analyses characterize molecular processes involved in disease pathology [3]. However, these modalities are often studied separately. Here we integrated neuroimaging and omics data to investigate how molecular signatures relate to brain alterations during PD progression.


Methods
We analyzed data from the Parkinson’s Progression Markers Initiative (PPMI) [4], a longitudinal study including de novo PD patients, prodromal individuals, and healthy controls. Subjects were selected if both brain imaging and molecular measurements were available, including cerebrospinal fluid proteomics or whole-blood RNA-seq data collected at different disease stages. Differential gene and protein expression analyses were performed, followed by functional enrichment analysis. In parallel, quantitative features such as contrast ratios and volumes of neuromelanin-rich areas were extracted from 2D gradient echo (GRE) brain images with magnetization transfer (MT). Associations between omics and imaging-derived features were then evaluated.

Results
A subset of genes and proteins showed significant associations with imaging features reflecting brain alterations typically observed in Parkinson’s disease. These findings suggest that disease progression is reflected by both molecular and imaging signatures. Further analysis revealed that progression does not follow a simple linear trajectory but instead involves distinct stages. Moreover, patterns of molecular and structural changes differed between sexes, highlighting heterogeneity in disease progression and suggesting potential sex-specific mechanisms.

Discussion
These findings highlight the value of integrating imaging and omics data to better characterize PD progression. Linking molecular signatures with structural brain alterations may improve our understanding of disease mechanisms and support the development of multimodal biomarkers for monitoring disease evolution.


References
[1]: Kalia, L. V., & Lang, A. E. (2015). Parkinson’s disease. The Lancet, 386(9996), 896–912.
[2]: He, H., et al. (2020). Progressive brain changes in Parkinson’s disease: A meta-analysis of structural magnetic resonance imaging studies. Brain Research Bulletin, 164, 272–279.
[3]: Sharma, S., & Dhamija, R. K. (2025). The quest for Parkinson’s disease biomarkers: Traditional and emerging multi-omics approaches. Molecular Biology Reports, 52, Article 831.
[4]: Parkinson’s Progression Markers Initiative (PPMI). https://www.ppmi-info.org

Acknowledgement
Data were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org). PPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners.