{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:19:01Z","timestamp":1791587941287,"version":"4.3.4"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Abnormal deposition of \u03b1-synuclein is a key feature and biomarker of Parkinson\u2019s disease. \u03b1-Synuclein aggregates can propagate themselves by a prion-like seeding-based mechanism within and between tissues and are hypothesized to move between the intestine and brain. \u03b1-Synuclein RT-QuIC seed amplification assays have detected Parkinson\u2019s-associated \u03b1-synuclein in multiple biospecimens including post-mortem colon samples. Here we show <jats:italic>intra vitam<\/jats:italic> detection of seeds in duodenum biopsies from 22\/23 Parkinson\u2019s patients, but not in 6 healthy controls by RT-QuICR. In contrast, no tau seeding activity was detected in any of the biopsies. Our seed amplifications provide evidence that the upper intestine contains a form(s) of \u03b1-synuclein with self-propagating activity. The diagnostic sensitivity and specificity for PD in this biopsy panel were 95.7% and 100% respectively. End-point dilution analysis indicated up to 10<jats:sup>6<\/jats:sup> SD<jats:sub>50<\/jats:sub> seeding units per mg of tissue with positivity in two contemporaneous biopsies from individual patients suggesting widespread distribution within the superior and descending parts of duodenum. Our detection of \u03b1-synuclein seeding activity in duodenum biopsies of Parkinson\u2019s disease patients suggests not only that such analyses may be useful in ante-mortem diagnosis, but also that the duodenum may be a source or a destination for pathological, self-propagating \u03b1-synuclein assemblies.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011456","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T17:22:38Z","timestamp":1688145758000},"page":"e1011456","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":41,"title":["\u03b1-Synuclein seeding activity in duodenum biopsies from Parkinson\u2019s disease patients"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6493-8669","authenticated-orcid":true,"given":"Sarah","family":"Vascellari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina D.","family":"Orr\u00f9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley R.","family":"Groveman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabiha","family":"Parveen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Fenu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Pisano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Piga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Serra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Oppo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Murgia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Perra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Angius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Hughson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathryn L.","family":"Haigh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Manzin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Cossu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Caughey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"issue":"2","key":"ppat.1011456.ref001","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson\u2019s disease","volume":"24","author":"H. 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Cersosimo","year":"2012","journal-title":"Neurobiol Dis"},{"issue":"1","key":"ppat.1011456.ref005","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.parkreldis.2010.08.003","article-title":"Gastrointestinal dysfunction in Parkinson\u2019s disease","volume":"17","author":"R.F. Pfeiffer","year":"2011","journal-title":"Parkinsonism Relat Disord"},{"issue":"5","key":"ppat.1011456.ref006","article-title":"Preclinical Detection of Alpha-Synuclein Seeding Activity in the Colon of a Transgenic Mouse Model of Synucleinopathy by RT-QuIC.","volume":"13","author":"J.Y. Han","year":"2021","journal-title":"Viruses"},{"key":"ppat.1011456.ref007","doi-asserted-by":"crossref","first-page":"105557","DOI":"10.1016\/j.nbd.2021.105557","article-title":"Neuropathological evidence of body-first vs. brain-first Lewy body disease","volume":"161","author":"P. Borghammer","year":"2021","journal-title":"Neurobiol Dis"},{"issue":"10","key":"ppat.1011456.ref008","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1093\/brain\/awaa238","article-title":"Brain-first versus body-first Parkinson\u2019s disease: a multimodal imaging case-control study","volume":"143","author":"J. Horsager","year":"2020","journal-title":"Brain"},{"key":"ppat.1011456.ref009","doi-asserted-by":"crossref","first-page":"105626","DOI":"10.1016\/j.nbd.2022.105626","article-title":"Clinical and imaging evidence of brain-first and body-first Parkinson\u2019s disease","volume":"164","author":"J. Horsager","year":"2022","journal-title":"Neurobiol Dis"},{"key":"ppat.1011456.ref010","doi-asserted-by":"crossref","first-page":"105599","DOI":"10.1016\/j.nbd.2021.105599","article-title":"Animal models of brain-first and body-first Parkinson\u2019s disease","author":"N. 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Fairfoul","year":"2016","journal-title":"Ann Clin Transl Neurol"},{"issue":"1","key":"ppat.1011456.ref019","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40478-018-0508-2","article-title":"Rapid and ultra-sensitive quantitation of disease-associated alpha-synuclein seeds in brain and cerebrospinal fluid by alphaSyn RT-QuIC","volume":"6","author":"B.R. Groveman","year":"2018","journal-title":"Acta Neuropathol Commun"},{"issue":"1","key":"ppat.1011456.ref020","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/s41531-021-00242-2","article-title":"Diagnostic value of skin RT-QuIC in Parkinson\u2019s disease: a two-laboratory study","volume":"7","author":"A. 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Russo","year":"2021","journal-title":"Acta Neuropathol Commun"},{"issue":"2","key":"ppat.1011456.ref026","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1001\/jamaneurol.2016.4547","article-title":"Development of a Biochemical Diagnosis of Parkinson Disease by Detection of alpha-Synuclein Misfolded Aggregates in Cerebrospinal Fluid","volume":"74","author":"M. Shahnawaz","year":"2017","journal-title":". JAMA Neurol"},{"key":"ppat.1011456.ref027","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.nbd.2019.05.002","article-title":"Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification","volume":"129","author":"A. Fenyi","year":"2019","journal-title":"Neurobiol Dis"},{"issue":"1","key":"ppat.1011456.ref028","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s40478-021-01175-w","article-title":"Streamlined alpha-synuclein RT-QuIC assay for various biospecimens in Parkinson\u2019s disease and dementia with Lewy bodies","volume":"9","author":"C. Bargar","year":"2021","journal-title":"Acta Neuropathol Commun"},{"issue":"2","key":"ppat.1011456.ref029","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/acn3.51280","article-title":"A rapid alpha-synuclein seed assay of Parkinson\u2019s disease CSF panel shows high diagnostic accuracy","volume":"8","author":"C.D. Orru","year":"2021","journal-title":"Ann Clin Transl Neurol"},{"issue":"1","key":"ppat.1011456.ref030","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12987-022-00368-2","article-title":"In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome","volume":"19","author":"G. Giannini","year":"2022","journal-title":"Fluids Barriers CNS"},{"issue":"1","key":"ppat.1011456.ref031","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s40478-022-01388-7","article-title":"Performance of alphaSynuclein RT-QuIC in relation to neuropathological staging of Lewy body disease","volume":"10","author":"S. 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Twohig","year":"2019","journal-title":"Mol Neurodegener"},{"issue":"1","key":"ppat.1011456.ref035","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s40478-020-0887-z","article-title":"A single ultrasensitive assay for detection and discrimination of tau aggregates of Alzheimer and Pick diseases","volume":"8","author":"M.A. Metrick","year":"2020","journal-title":"Acta Neuropathol Commun"},{"issue":"9","key":"ppat.1011456.ref036","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.02162-16","article-title":"Endogenous Brain Lipids Inhibit Prion Amyloid Formation In Vitro","volume":"91","author":"C.E. Hoover","year":"2017","journal-title":"J Virol"},{"issue":"4","key":"ppat.1011456.ref037","volume":"12","author":"A. Srivastava","year":"2022","journal-title":"RT-QuIC and Related Assays for Detecting and Quantifying Prion-like Pathological Seeds of alpha-Synuclein. Biomolecules"},{"issue":"1","key":"ppat.1011456.ref038","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s12264-012-1050-z","article-title":"Progression of motor symptoms in Parkinson\u2019s disease","volume":"28","author":"R. Xia","year":"2012","journal-title":"Neurosci Bull"},{"key":"ppat.1011456.ref039","doi-asserted-by":"crossref","first-page":"853050","DOI":"10.3389\/fnagi.2022.853050","article-title":"Real-Time Quaking- Induced Conversion Assays for Prion Diseases, Synucleinopathies, and Tauopathies","volume":"14","author":"S. Vascellari","year":"2022","journal-title":"Front Aging Neurosci"},{"issue":"1","key":"ppat.1011456.ref040","doi-asserted-by":"crossref","DOI":"10.4172\/2161-1149.1000235","article-title":"Gastrointestinal Manifestations of Systemic Sclerosis","volume":"8","author":"I.M. McFarlane","year":"2018","journal-title":"Rheumatology (Sunnyvale)"},{"issue":"1","key":"ppat.1011456.ref041","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/rheumatology\/kel203","article-title":"Outcome of small-bowel motor impairment in systemic sclerosis\u2014a prospective manometric 5-yr follow-up","volume":"46","author":"I. Marie","year":"2007","journal-title":"Rheumatology (Oxford)"},{"issue":"15","key":"ppat.1011456.ref042","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1212\/WNL.0000000000004496","article-title":"REM sleep behavior disorder is related to enteric neuropathology in Parkinson disease","volume":"89","author":"L. 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Agachan","year":"1996","journal-title":"Dis Colon Rectum"},{"key":"ppat.1011456.ref046","first-page":"5 23 1","article-title":"Autoinduction of protein expression","author":"B.G. Fox","year":"2009","journal-title":"Curr Protoc Protein Sci"},{"key":"ppat.1011456.ref047","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/978-1-4939-2978-8_9","article-title":"Formation and Characterization of alpha-Synuclein Oligomers","volume":"1345","author":"W. Paslawski","year":"2016","journal-title":". Methods Mol Biol"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011456","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T17:23:14Z","timestamp":1688145794000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011456"}},"subtitle":[],"editor":[{"given":"Amanda L.","family":"Woerman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,6,30]]},"references-count":47,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011456","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,30]]}}}