{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:38:06Z","timestamp":1793140686145,"version":"4.5.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Finnish Parkinson Foundation"},{"name":"the Turku University Foundation"},{"name":"the Finnish Brain Foundation"},{"name":"the Maire Taponen Foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Levodopa remains the cornerstone of treatment in Parkinson\u2019s disease (PD), but its long-term impact on neuroinflammation remains unclear, particularly in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), where levodopa efficacy is limited. This study examined whether chronic levodopa exposure is associated with neuroinflammation or dopaminergic neuronal loss in end-stage PD, MSA, and PSP. Postmortem midbrain tissue from 63 neuropathologically confirmed cases (PD:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200938; PSP:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200913; MSA:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912) was analyzed. Immunohistochemistry was used to quantify tyrosine hydroxylase positive (TH+) neurons in the substantia nigra pars compacta (SNc), along with T lymphocyte (CD3+, CD4+, CD8+) infiltration and microglial density (Iba1 expression). Levodopa exposure was estimated using three models and analyzed in relation to neuropathological markers, adjusting for age at death, sex, disease duration, and Hoehn &amp; Yahr stage. Results. No significant associations were observed between levodopa exposure and TH\u2009+\u2009neuronal density or T cell infiltration or microglial density. For example, in PD, mean daily levodopa dose was not associated with CD3\u2009+\u2009T cell density (\u03b2\u2009=\u20092.06\u2009\u00d7\u200910\u207b\u2075, 95%CI: \u22120.001 to 0.001,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.96). Chronic levodopa use was not associated with persistent neuroinflammation or dopaminergic neuronal loss at end-stage disease, suggesting no long-term immune-mediated toxicity in the substantia nigra.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-23376-2","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T18:28:14Z","timestamp":1762885694000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Levodopa exposure and nigral neuroinflammation in parkinsonian disorders: A postmortem study of 63 cases"],"prefix":"10.1038","volume":"15","author":[{"given":"Emmilotta A.","family":"Backman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Luntamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tero","family":"Vahlberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gardberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valtteri","family":"Kaasinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"23376_CR1","doi-asserted-by":"publisher","first-page":"S249","DOI":"10.1007\/s00415-010-5741-y","volume":"257","author":"O Hornykiewicz","year":"2010","unstructured":"Hornykiewicz, O. A brief history of Levodopa. J. Neurol. 257, S249\u2013252 (2010).","journal-title":"J. Neurol."},{"issue":"Suppl 3","key":"23376_CR2","doi-asserted-by":"publisher","first-page":"S497","DOI":"10.1002\/mds.22028","volume":"23","author":"S Fahn","year":"2008","unstructured":"Fahn, S. The history of dopamine and Levodopa in the treatment of parkinson\u2019s disease. Mov. Disord. 23 (Suppl 3), S497\u2013508 (2008).","journal-title":"Mov. Disord"},{"key":"23376_CR3","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1002\/mds.26082","volume":"30","author":"PA LeWitt","year":"2015","unstructured":"LeWitt, P. A. Levodopa therapy for parkinson\u2019s disease: pharmacokinetics and pharmacodynamics. Mov. Disord. 30, 64\u201372 (2015).","journal-title":"Mov. Disord"},{"key":"23376_CR4","doi-asserted-by":"crossref","unstructured":"Ye, L. et al. Acute Levodopa challenge in atypical parkinsonism: comprehensive analysis of individual motor responses. 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As this was a retrospective postmortem study utilizing archived clinical and neuropathological data without patient contact, the requirement for informed consent was formally waived by the ethics committee.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"39516"}}