{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:02:57Z","timestamp":1790056977466,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS\u20102023\u201000265159"],"award-info":[{"award-number":["RS\u20102023\u201000265159"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n \u03b1<\/jats:italic>\n \u2010Synuclein aggregation is a pathological hallmark of synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy (MSA). Although pathogenic\n \u03b1<\/jats:italic>\n \u2010synuclein seeds can be detected by real\u2010time quaking\u2010induced conversion (RT\u2010QuIC), current assays primarily rely on cerebrospinal fluid, whose invasiveness limits repeated and large\u2010scale applications. We therefore evaluated the feasibility of detecting pathogenic\n \u03b1<\/jats:italic>\n \u2010synuclein using urine\u2010derived neuronal extracellular vesicles (NEVs).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Urine\u2010derived NEVs were enriched by direct immunoprecipitation using L1CAM\u2010conjugated magnetic beads. The RT\u2010QuIC assay was performed in 26 patients with PD, 13 with MSA, and 25 disease controls, including 16 healthy controls (HC), 4 with progressive supranuclear palsy (PSP), and 5 with normal pressure hydrocephalus (NPH).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Urine\u2010derived NEVs exhibited characteristic neuronal and exosomal markers and a typical extracellular vesicle size distribution. The urine\u2010based RT\u2010QuIC assay distinguished PD from disease controls with 73.1% sensitivity and 84% specificity, and MSA from disease controls with 76.9% sensitivity and 84% specificity. When compared with HC alone, sensitivity and specificity were 73.1% and 93.8% for PD, and 76.9% and 93.8% for MSA, respectively. Kinetic analysis showed higher maximum fluorescence intensity and area under the curve (AUC) in PD compared with both disease controls and HC (\n P<\/jats:italic>\n \u2009<\u20090.001 in all). MSA also demonstrated higher maximum fluorescence intensity than HC and increased AUC compared with both disease controls and HC (\n P<\/jats:italic>\n \u2009<\u20090.05 in all).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We developed and optimized a completely non\u2010invasive urine\u2010derived NEV\n \u03b1<\/jats:italic>\n \u2010synuclein RT\u2010QuIC assay that demonstrates high specificity and moderate sensitivity for synucleinopathies. This approach warrants further validation in larger cohorts. \u00a9 2026 International Parkinson and Movement Disorder Society.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mds.70533","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:30:39Z","timestamp":1790055039000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Urine\u2010Derived Neuronal Extracellular Vesicle\n \n \u03b1<\/i>\n <\/scp>\n \u2010Synuclein Seed Amplification Assay for Synucleinopathies: A Non\u2010Invasive Biomarker Study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9940-8685","authenticated-orcid":false,"given":"Hoang Bao Tram","family":"Tran","sequence":"first","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine Anyang Republic of Korea"},{"name":"Department of Medical Sciences Graduate School of Hallym University Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2491-5566","authenticated-orcid":false,"given":"Huu Dat","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine Anyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3430-9443","authenticated-orcid":false,"given":"Thanh Trung","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine Anyang Republic of Korea"},{"name":"Department of Medical Sciences Graduate School of Hallym University Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Joung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine Anyang Republic of Korea"},{"name":"Department of Medical Sciences Graduate School of Hallym University Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk\u2010Jun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine Anyang Republic of Korea"},{"name":"Department of Medical Sciences Graduate School of Hallym University Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5968-7199","authenticated-orcid":false,"given":"In Hee","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine Anyang Republic of Korea"},{"name":"Hallym Neurological Institute, Hallym University Anyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9597-8436","authenticated-orcid":false,"given":"Dong Gyun","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine Anyang Republic of Korea"},{"name":"Hallym Neurological Institute, Hallym University Anyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Hyun","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine Anyang Republic of Korea"},{"name":"Hallym Neurological Institute, Hallym University Anyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Je Kook","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine Anyang Republic of Korea"},{"name":"Hallym Neurological Institute, Hallym University Anyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6733-9779","authenticated-orcid":false,"given":"Hyeo\u2010il","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine Anyang Republic of Korea"},{"name":"Hallym Neurological Institute, Hallym University Anyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-6569","authenticated-orcid":false,"given":"Young Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine Anyang Republic of Korea"},{"name":"Hallym Neurological Institute, Hallym University Anyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"issue":"6","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s00702-023-02653-2","article-title":"The \u2018\u03b1\u2010synucleinopathy syndicate\u2019: multiple system atrophy and Parkinson's disease","volume":"131","author":"Sian\u2010Hulsmann 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Cold Spring Harbor Laboratory;2025.","DOI":"10.1101\/2025.07.17.665403"},{"issue":"36","key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"13368","DOI":"10.1073\/pnas.0403453101","article-title":"Identification and proteomic profiling of exosomes in human urine","volume":"101","author":"Pisitkun T","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"e_1_2_10_26_1","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.tips.2025.03.006","article-title":"Monitoring neurodegeneration through brain\u2010derived extracellular vesicles in biofluids","volume":"46","author":"Torrini F","year":"2025","journal-title":"Trends Pharmacol Sci"},{"issue":"8","key":"e_1_2_10_27_1","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aeb0555","article-title":"Glomerular routing of tumor\u2010derived extracellular vesicles substantiates urinary biopsy","volume":"12","author":"Kawaguchi S","year":"2026","journal-title":"Sci 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