Peripheral and central dysregulation of the kynurenine pathway in Parkinson's disease

Peripheral and central dysregulation of the kynurenine pathway in Parkinson's disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Peripheral and central dysregulation of the kynurenine pathway in Parkinson's disease Leslie C Jellen, Martha L Escobar Galvis, Qiong Sha, Christine Isaguirre, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5434393/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 May, 2025 Read the published version in npj Parkinson's Disease → Version 1 posted 12 You are reading this latest preprint version Abstract We previously demonstrated that kynurenine pathway (KP) dysregulation is associated with Parkinson’s disease (PD) and its symptoms. Here, we profiled 16 KP-related markers in a second, independent cohort; plasma: n=202 (116 PD (“OFF”), 86 controls); CSF: n=183. Consistent with previous findings, we detected significantly higher concentrations of neurotoxic 3-hydroxykynurenine in plasma and lower concentrations of neuroprotective kynurenic acid along with higher neurotoxic quinolinic acid/kynurenic acid ratios in CSF of PD patients. Additionally, 10 markers showed sex-based differences, with more pronounced dysregulation in female patients. These markers loaded to a single principal component linked to higher UPDRS I and II scores. Together, this suggests a composite signature of KP dysregulation in PD associated with worse non-motor and motor symptoms and more prevalent in women. This work shows that KP dysregulation in peripheral and central compartments is linked to symptom severity in PD and warrants further systematic studies unraveling sex-dependent metabolic differences. Health sciences/Diseases/Neurological disorders/Movement disorders Health sciences/Diseases/Neurological disorders/Neurodegenerative diseases Health sciences/Diseases/Neurological disorders/Parkinsons disease tryptophan inflammation biomarkers PD sex differences Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryData1.xlsx SupplementaryData2.xlsx Cite Share Download PDF Status: Published Journal Publication published 06 May, 2025 Read the published version in npj Parkinson's Disease → Version 1 posted Editorial decision: Revision requested 23 Dec, 2024 Reviews received at journal 01 Dec, 2024 Reviews received at journal 27 Nov, 2024 Reviews received at journal 25 Nov, 2024 Reviewers agreed at journal 18 Nov, 2024 Reviewers agreed at journal 18 Nov, 2024 Reviewers agreed at journal 17 Nov, 2024 Reviewers agreed at journal 15 Nov, 2024 Reviewers invited by journal 15 Nov, 2024 Editor assigned by journal 12 Nov, 2024 Submission checks completed at journal 11 Nov, 2024 First submitted to journal 11 Nov, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5434393","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":383550479,"identity":"f393b7f3-24a3-4b8e-93fe-66b00e21b58c","order_by":0,"name":"Leslie C Jellen","email":"","orcid":"","institution":"Pennsylvania State University","correspondingAuthor":false,"prefix":"","firstName":"Leslie","middleName":"C","lastName":"Jellen","suffix":""},{"id":383550480,"identity":"fcee364b-5601-4d9b-b7f5-430f49feb493","order_by":1,"name":"Martha L Escobar Galvis","email":"","orcid":"","institution":"Van Andel 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