Identification of circulatory neuro-related proteins in Parkinson's disease: an integrated genetic–proteomic–clinical study
eBioMedicine, 2026
Zhou H., Wang Z., Tan Z., Deng B., Yang W., Huang Z., Guo X., Li J., Wang X., Yu Y., Deng C., Zheng W., Zhang X., Chen X., Yue J., Yang C., Cui X., Poplawska-Domaszewicz K., Chaudhuri K., Zhou Z., Xiao B., Chan L., Foo J., Tan E., Wang Q.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Background
Neuro-related proteins are promising biomarkers and therapeutic targets for Parkinson’s disease (PD), yet their specific roles remain uncertain.
Methods
We conducted Mendelian randomisation by integrating protein quantitative trait loci with genome-wide association study data from 33,647 patients with PD and 449,056 controls for risk, 28,568 patients for age at onset (AAO), and 4093 patients for progression. Subsequent analyses included genetic colocalisation, protein–protein interaction, functional enrichment, tissue and cell-specific expression profiling, and druggability assessment. In an case–control study (30 patients with PD, 14 controls), plasma neuro-related proteins were measured using the Olink platform.
Findings
59 neuro-related proteins were associated with PD: 4 (CLEC1B, IL5RA, SNCG, CDH17) associated with risk, 7 with AAO, and 58 with progression. Colocalisation supported shared variants for TDGF1, PVR, and IL5RA with the progression. 47 proteins were evaluated as druggable targets. Pathway analysis highlighted cytokine–receptor interactions, neuroimmune modulation, and axon guidance. BMP-4, DDR1, GDNF, LAT, and MANF were found to be differentially expressed in patients with PD and correlated with the symptom severity.
Interpretation
This integrative genetic–proteomic–clinical framework identifies neuro-related proteins significantly associated with PD, offering mechanistic insights and prioritising therapeutic targets.