{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:31:40Z","timestamp":1793035900751,"version":"4.5.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>An involvement of the central-nervous and peripheral, innate and adaptive immune system in the pathogenesis of Parkinson's disease (PD) is nowadays well established.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We face several open questions in preparation of clinical trials aiming at disease-modification by targeting the immune system: Do peripheral (blood) inflammatory profiles reflect central (CSF) inflammatory processes? Are blood\/CSF inflammatory markers associated with CSF levels of neurodegenerative\/PD-specific biomarkers?<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a multiplex assay we assessed 41 inflammatory markers in CSF\/serum pairs in 453 sporadic PD patients. We analyzed CSF\/serum correlation as well as associations of inflammatory markers with clinical outcome measures (UPDRS-III, H&amp;amp;Y, MoCA) and with CSF levels of \u03b1-synuclein, A\u03b2<jats:sub>1\u221242<\/jats:sub>, <jats:italic>t-<\/jats:italic>Tau, p181-Tau and NFL. All analyses were stratified by sex as the immune system shows relevant sex-specific differences.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Correlations between CSF and serum were sparse and detected in only 25% (9 out of 36) of the analysable inflammatory markers in male PD patients and in only 38% (12 out of 32) of female PD patients. The most important pro-inflammatory mediators associated with motor and cognitive decline as well as with neurodegenerative\/PD-specific biomarkers were FABP, ICAM-1, IL-8, MCP-1, MIP-1-beta, and SCF. Results were more robust for CSF than for serum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Levels of central-nervous and peripheral inflammatory markers might be regulated independently of each other with CSF inflammatory markers reflecting CNS pathology more accurately than peripheral markers. These findings along with sex-specific characteristics have to be considered when designing clinical trials aiming at disease-modification by targeting the immune system.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.834580","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T10:04:54Z","timestamp":1645783494000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["CSF and Serum Levels of Inflammatory Markers in PD: Sparse Correlation, Sex Differences and Association With Neurodegenerative Biomarkers"],"prefix":"10.3389","volume":"13","author":[{"given":"Stefanie","family":"Lerche","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Wurster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Roeben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca Laura","family":"Fries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Deuschle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Waniek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingolf","family":"Lachmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meike","family":"Jakobi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Joos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Schneiderhan-Marra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Brockmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1038\/ng.3043","article-title":"Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease","volume":"46","author":"Nalls","year":"2014","journal-title":"Nat Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1002\/mds.23455","article-title":"Glia: initiators and progressors of pathology in Parkinson's disease","volume":"26","author":"Halliday","year":"2011","journal-title":"Mov Disord"},{"key":"B3","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1002\/mds.26563","article-title":"Serum immune markers and disease progression in an incident Parkinson's disease cohort (ICICLE-PD)","volume":"31","author":"Williams-Gray","year":"2016","journal-title":"Movement Disord."},{"key":"B4","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1001\/jamaneurol.2017.0469","article-title":"International Parkinson's Disease Genomics Consortium, and I. 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