Objective: To identify diagnostic and progression biomarkers in the longitudinal DeNoPa cohort of (at enrolment) de novo Parkinson’s disease (PD) and healthy controls (HC) using multiplex panels of 92 inflammatory markers to elucidate the effect of inflammatory processes in the disease course.
Background: Objective diagnostic and progression biomarkers are needed to possibly support the clinical diagnosis of early PD and optimize patient inclusion into clinical trials. The role of inflammation in disease progression needs to be investigated for possible interventional targets.
Method: EDTA plasma samples from DeNoPa of 96 HC subjects (baseline) and 4 years follow-up as well as from 109 PD subjects (baseline) up to 8-years follow-up were analyzed using the proximity extension assay technology on 92 neuroinflammatory markers. Further, samples (26 HC, 42 PD) of cerebrospinal fluid (CSF) were added. A threshold of 60 % missing (below limit of detection, LOD) was used for keeping a protein in the downstream analysis; missing values of those above 60% detection have been imputed if the protein passes the threshold. Multiple testing was used to test the different expression for significance. A total of 49 markers (53%) in CSF and 28 markers (30%) in plasma were below LOD.
Results: We identified 4 marker candidates in plasma, that were differently expressed between HC and PD including FMS-like tyrosine kinase 3 ligand(Flt3L), Urokinase-type plasminogen activator(uPA), Fibroblast growth factor 21 (FGF-21) and C-X-C Motif Chemokine Ligand 5(CXCL5). In CSF no marker with different expression on significance level of 5 % was found, on level 16 %, C-X-C Motif Chemokine Ligand 6(CXCL6), C-C Motif Chemokine Ligand 19(CCL19) and CXCL5 could be detected.
Conclusion: From 92 markers, some identified have already been described in the context of ageing (FGF-21, uPA), differentiation between PD and atypical Parkinson syndromes (Flt3L), vascular diseases (CCL19), neurogenesis (CXCL6) and brain injury (CXCL5). The platform did show few significant differences in inflammatory parameters between PD and HC. Further investigation of inflammatory processes and their relevance in PD including the validation in larger, independent cohorts is needed to clarify if the results are rather assay specific or identified only a subtle inflammatory response in PD.
References: 1: Yilmaz R, Strafella AP, Bernard A, Schulte C, van den Heuvel L, Schneiderhan-Marra N, Knorpp T, Joos TO, Leypoldt F, Geritz J, Hansen C, Heinzel S, Apel A, Gasser T, Lang AE, Berg D, Maetzler W, Marras C. Serum Inflammatory Profile for the Discrimination of Clinical Subtypes in Parkinson’s Disease. Front Neurol. 2018 Dec 21;9:1123. doi: 10.3389/fneur.2018.01123. eCollection 2018. PubMed PMID: 30622507; PubMed Central PMCID: PMC6308160.
To cite this abstract in AMA style:
M. Bartl, M. Dakna, S. Schade, B. Otte, C. Trenkwalder, B. Mollenhauer. Multiplex biomarker discovery for diagnostic and progression markers for Parkinson’s disease with the proximity extension assay technology on inflammation-related analytes [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/multiplex-biomarker-discovery-for-diagnostic-and-progression-markers-for-parkinsons-disease-with-the-proximity-extension-assay-technology-on-inflammation-related-analytes/. Accessed May 15, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/multiplex-biomarker-discovery-for-diagnostic-and-progression-markers-for-parkinsons-disease-with-the-proximity-extension-assay-technology-on-inflammation-related-analytes/