{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:58:47Z","timestamp":1792677527592,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,5,8]],"date-time":"2018-05-08T00:00:00Z","timestamp":1525737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000304","name":"Parkinson's UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. 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To increase sensitivity and specificity, we applied three techniques to detect different conformations of aSyn in <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> biopsies obtained from a longitudinal, clinically well\u2010characterized cohort of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> patients and healthy controls (<jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>With immunohistochemistry (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>), we used antibodies reactive for total, phosphorylated and oligomeric <jats:styled-content style=\"fixed-case\">aS<\/jats:styled-content>yn; with <jats:styled-content style=\"fixed-case\">aS<\/jats:styled-content>yn proximity ligation assay (<jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PLA<\/jats:styled-content>), we targeted oligomeric <jats:styled-content style=\"fixed-case\">aS<\/jats:styled-content>yn species specifically; and with paraffin\u2010embedded tissue blot (<jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PET<\/jats:styled-content>\u2010blot) we aimed to detect fibrillary, synaptic <jats:styled-content style=\"fixed-case\">aS<\/jats:styled-content>yn.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 163 tissue blocks were collected from 51 <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> patients (113 blocks) and 21 <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content> (50 blocks). In 31 <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> patients, biopsies were taken before the <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> diagnosis (Prodromal); while in 20 <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> patients biopsies were obtained after diagnosis (Manifest). The majority of tissues blocks were from large intestine (62%), followed by small intestine (21%), stomach (10%) and oesophagus (7%). With <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>, four staining patterns were detected (<jats:italic>neuritic, ganglionic, epithelial and cellular<\/jats:italic>), while two distinct staining patterns were detected both with <jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PLA<\/jats:styled-content> (<jats:italic>cellular<\/jats:italic> and <jats:italic>diffuse<\/jats:italic> signal) and with <jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PET<\/jats:styled-content>\u2010blot (<jats:italic><jats:styled-content style=\"fixed-case\">aS<\/jats:styled-content>yn\u2010localized<\/jats:italic> and <jats:italic>pericrypt<\/jats:italic> signal). The level of agreement between different techniques was low and no single technique or staining pattern reliably distinguished <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> patients (Prodromal or Manifest) from <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study suggests that detection of <jats:styled-content style=\"fixed-case\">aS<\/jats:styled-content>yn conformational variants currently considered pathological is not adequate for the diagnosis or prediction of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>. Future studies utilizing novel ultrasensitive amyloid aggregation assays may increase sensitivity and specificity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12486","type":"journal-article","created":{"date-parts":[[2018,4,20]],"date-time":"2018-04-20T02:05:06Z","timestamp":1524189906000},"page":"722-736","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Detection of alpha\u2010synuclein conformational variants from gastro\u2010intestinal biopsy tissue as a potential biomarker for Parkinson's disease"],"prefix":"10.1111","volume":"44","author":[{"given":"C.","family":"Ruffmann","sequence":"first","affiliation":[{"name":"Oxford Parkinson's Disease Centre Nuffield Department of Clinical Neurosciences University of Oxford John Radcliffe Hospital Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Bengoa\u2010Vergniory","sequence":"additional","affiliation":[{"name":"Oxford Parkinson's Disease Centre Department of Physiology, Anatomy and Genetics University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Poggiolini","sequence":"additional","affiliation":[{"name":"Oxford Parkinson's Disease Centre Nuffield Department of Clinical Neurosciences University of Oxford John Radcliffe Hospital Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Ritchie","sequence":"additional","affiliation":[{"name":"National CJD Research &amp; Surveillance Unit Centre for Clinical Brain Sciences Deanery of Clinical Medicine University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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