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Plasminogen activator inhibitor-1 (SERPIN E1) is known for its association with aging processes and exacerbated \u03b1-Synuclein pathology. We examined whether SERPIN E1 levels in cerebrospinal fluid (CSF) differ among controls (CON, <jats:italic>N<\/jats:italic>\u2009=\u200916) and patients with PD (<jats:italic>N<\/jats:italic>\u2009=\u2009479) or Dementia with Lewy bodies (DLB, <jats:italic>N<\/jats:italic>\u2009=\u200967), considering that these conditions represent a spectrum of \u03b1-Synuclein pathology. Kaplan-Meier survival analysis stratified by SERPIN E1 tertile levels was conducted to evaluate phenotype-modifying effects. Elevated levels of SERPIN E1 exhibited an association with increased age and lower MOCA scores. Heightened SERPIN E1 levels were observed in individuals diagnosed with DLB, followed by PD and CON, and in males compared to females. 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K.B. received Research Grants from the Michael J Fox Foundation for Parkinson\u2019s Research (\u201cLRRK2 Kinase Activity\u201d,\u201cInfluence of Inflammatory Profiles on PD Phenotype and Progression\u201d, \u201cPrevent Dementia in GBA1-associated PD\u201d), from the University of Tuebingen (\u201cEndophenotyping of GBA1-PD\u201d), from the German Society for Parkinson DPG, from the Health Forum Baden Wuerttemberg (\u201cPredictive Diagnostic of immune-associated diseases for personalised medicine\u201d, AZ 35-4223.10\/8), from the Else Kr\u00f6ner Fresenius Stiftung (\u201cClinBrain\u201d), and from the German Research Foundation DFG (\u201cCORO-TREND\u201d). She serves on advisory boards for F. Hoffmann-La Roche Ltd and VanqaBio. She received speaker honoraria from Abbvie, Lundbeck, UCB and Zambon. C.D. has nothing to disclose. T.G. serves on the editorial board of the Journal of PD. He holds a patent re: KASPP (LRRK2) gene, its production and use for the detection and treatment of neurodegenerative diseases. Prof. Gasser has received speaker\u2019s honoraria from UCB Pharma, Novartis, Sanofi and MedUpdate. He has received consulting fees from Bayer AG, BlueRock Therapeutics and Biogen. He is Chairman of the Scientific Advisory Board of the \u201cJoint Programming for Neurodegenerative Diseases\u201d program, funded by the European Commission. He has received grant support from the German Research Foundation (DFG), the German Federal Ministry of Education and Research (BMBF), the Ministry for Science, Research and Art Baden-W\u00fcrttemberg (MWK), the European Commission, the Helmholtz Association and The Michael J. Fox Foundation. M.F. has nothing to disclose. M.J. has nothing to disclose. T.J. has nothing to disclose. S.L. has nothing to disclose. B.R. has received a research grant from the University of Tuebingen (Clinician Scientist; Project-Nr. 480-0-0). N.S.M. has received funding from the State Ministry of Baden-W\u00fcrttemberg for Economic Affairs, Labour and Tourism (\u201cPredictive Diagnostic of immune-associated diseases for personalised medicine\u201d, AZ 35-4223.10\/8). C.S. has nothing to disclose. I.W. receives funding from The Michael J. Fox Foundation (MJFF) as an Edmond J. Safra Fellow in Movement Disorders. M.Z. has received a research grant from the University of Tuebingen (Clinician Scientist; Project-Nr. 481-0-0). S.Z. has nothing to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All participants gave written informed consent. The study was approved by the Ethics Committee of the Faculty of Medicine at the University of Tuebingen (Project-Nr. 458\/2023BO2). All procedures were in accordance with the Declaration of Helsinki (1975).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"166"}}