@article{a923263eca824a968462eaa15f0ac13c,
title = "Inflammatory Blood Biomarkers Are Associated with Long-Term Clinical Disease Severity in Parkinson{\textquoteright}s Disease",
abstract = "An altered immune response has been identified as a pathophysiological factor in Parkinson{\textquoteright}s disease (PD). We aimed to identify blood immunity-associated proteins that discriminate PD from controls and that are associated with long-term disease severity in PD patients. Immune response-derived proteins in blood plasma were measured using Proximity Extension Technology by OLINK in a cohort of PD patients (N = 66) and age-matched healthy controls (N = 52). In a selection of 30 PD patients, we evaluated changes in protein levels 7–10 years after the baseline and assessed correlations with motor and cognitive assessments. Data from the Parkinson{\textquoteright}s Disease Biomarkers Program (PDBP) cohort and the Parkinson{\textquoteright}s Progression Markers Initiative (PPMI) cohort were used for independent validation. PD patients showed an altered immune response compared to controls based on a panel of four proteins (IL-12B, OPG, CXCL11, and CSF-1). The expression levels of five inflammation-associated proteins (CCL23, CCL25, TNFRSF9, TGF-alpha, and VEGFA) increased over time in PD and were partially associated with more severe motor and cognitive symptoms at follow-up. Increased CCL23 levels were associated with cognitive decline and the APOE4 genotype. Our findings provide further evidence for an altered immune response in PD that is associated with disease severity in PD over a long period of time.",
keywords = "CCL23, Parkinson{\textquoteright}s disease, TGF-alpha, TNFRSF9, blood biomarkers, disease severity, immune response",
author = "Hepp, {Dagmar H.} and {van Wageningen}, {Thecla A.} and Kuiper, {Kirsten L.} and {van Dijk}, {Karin D.} and Oosterveld, {Linda P.} and Berendse, {Henk W.} and {van de Berg}, {Wilma D. J.}",
note = "Funding Information: No specific funding was used for the experiments/analysis described in the manuscript. We thank Stichting Woelse Waard en Health Holland for their financial support regarding the salary of D.H.H. and T.A.v.W. Funding Information: The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. Proteomic validation data used in the preparation of this article were obtained from the Accelerating Medicine Partnership (AMP) Parkinson{\textquoteright}s Disease (AMP PD) Knowledge Platform. For up-to-date information on the study, visit https://www.amp-pd.org accessed on 1 July 2023. The AMP PD program is a public–private partnership managed by the Foundation for the National Institutes of Health and funded by the National Institute of Neurological Disorders and Stroke (NINDS) in partnership with the Aligning Science Across Parkinson{\textquoteright}s (ASAP) initiative; Celgene Corporation, a subsidiary of Bristol-Myers Squibb Company; GlaxoSmithKline plc (GSK); The Michael J. Fox Foundation for Parkinson{\textquoteright}s Research; Pfizer Inc.; Sanofi US Services Inc.; and Verily Life Sciences. ACCELERATING MEDICINES PARTNERSHIP and AMP are registered service marks of the U.S. Department of Health and Human Services. {\textregistered} {\textregistered} {\textregistered} Publisher Copyright: {\textcopyright} 2023 by the authors.",
year = "2023",
month = oct,
day = "1",
doi = "https://doi.org/10.3390/ijms241914915",
language = "English",
volume = "24",
journal = "International journal of molecular sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "19",
}