Identification of circulatory neuro-related proteins in Parkinson's disease: an integrated genetic–proteomic–clinical study
Year: 2026
Type: article
Study design: Observational Study
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. FUNDING: National Natural Science Foundation of China (NO: U24A20694, NO: 82471433), and Scientific Research Foundation of Guangzhou (NO: 202206010005) to QW; and National Natural Science Foundation of China (NO: 82401641) to BD; and Basic and Applied Basic Research of Guangdong (NO: 2025A1515012456) to WLY; and Ministry of Education Academic Research Fund Tier 1 (RG111/24) to JNF; and National Medical Research Council grants to EKT.
Source: EBioMedicine
Authors: Hang Zhou, Zihao Wang, Zixin Tan, Bin Deng, Wanlin Yang, Zifeng Huang, Xingfang Guo, Jintao Li, Xinhao Wang, Yinghua Yu, Chao Deng, Wenhua Zheng, Xu Zhang, Xi Chen, Jianhui Yue, Chengwu Yang, Xiaoying Cui, Karolina Poplawska-Domaszewicz, K Ray Chaudhuri, Zhidong Zhou, Bin Xiao, Ling-Ling Chan, Jia Nee Foo, Eng-King Tan, Qing Wang
Institutions: Zhujiang Hospital, Southern Medical University, Jiangmen Central Hospital, University of Wollongong, University of Macau, University of Massachusetts Chan Medical School, The University of Queensland, Queensland Centre for Mental Health Research, Poznan University of Medical Sciences, King's College Hospital, National University of Singapore, Singapore General Hospital, Duke-NUS Medical School, National Neuroscience Institute, Nanyang Technological University, SingHealth Duke-NUS Academic Medical Centre
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,780
OpenAlex ID: W7130818831