{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:40:05Z","timestamp":1791430805867,"version":"4.3.3"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recent studies reported abnormal alpha\u2010synuclein deposition in biopsy\u2010accessible sites of the peripheral nervous system in Parkinson's disease (PD). This has considerable implications for clinical diagnosis. Moreover, if deposition occurs early, it may enable tissue diagnosis of prodromal PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this study was to develop and test an automated bright\u2010field immunohistochemical assay of cutaneous pathological alpha\u2010synuclein deposition in patients with idiopathic rapid eye movement sleep behavior disorder, PD, and atypical parkinsonism and in control subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>For assay development, postmortem skin biopsies were taken from 28 patients with autopsy\u2010confirmed Lewy body disease and 23 control subjects. Biopsies were stained for pathological alpha\u2010synuclein in automated stainers using a novel dual\u2010immunohistochemical assay for serine 129\u2010phosphorylated alpha\u2010synuclein and pan\u2010neuronal marker protein gene product 9.5. After validation, single 3\u2010mm punch skin biopsies were taken from the cervical 8 paravertebral area from 79 subjects (28 idiopathic rapid eye movement sleep behavior disorder, 20 PD, 10 atypical parkinsonism, and 21 control subjects). Raters blinded to clinical diagnosis assessed the biopsies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The immunohistochemistry assay differentiated alpha\u2010synuclein pathology from nonpathological\u2010appearing alpha\u2010synuclein using combined phosphatase and protease treatments. Among autopsy samples, 26 of 28 Lewy body samples and none of the 23 controls were positive. Among living subjects, punch biopsies were positive in 23 (82%) subjects with idiopathic rapid eye movement sleep behavior disorder, 14 (70%) subjects with PD, 2 (20%) subjects with atypical parkinsonism, and none (0%) of the control subjects. After a 3\u2010year follow\u2010up, eight idiopathic rapid eye movement sleep behavior disorder subjects phenoconverted to defined neurodegenerative syndromes, in accordance with baseline biopsy results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Even with a single 3\u2010mm punch biopsy, there is considerable promise for using pathological alpha\u2010synuclein deposition in skin to diagnose both clinical and prodromal PD. \u00a9 2020 International Parkinson and Movement Disorder Society<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.28399","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T00:30:59Z","timestamp":1606264259000},"page":"895-904","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Immunohistochemical Detection of Synuclein Pathology in Skin in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinsonism"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0019-8793","authenticated-orcid":false,"given":"Ahmed","family":"Al\u2010Qassabi","sequence":"first","affiliation":[{"name":"Department of Neurology McGill University\u2013Montreal General Hospital  Montreal Quebec Canada"},{"name":"Sultan Qaboos University Hospital  Muscat"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsu\u2010Shuen","family":"Tsao","sequence":"additional","affiliation":[{"name":"Roche Tissue Diagnostics  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Racolta","sequence":"additional","affiliation":[{"name":"Roche Tissue Diagnostics  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kremer","sequence":"additional","affiliation":[{"name":"Roche Pharmaceutical Research and Early Development, Roche Innovation Centre Basel F. Hoffmann\u2010La Roche Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ca\u00f1amero","sequence":"additional","affiliation":[{"name":"Roche Pharmaceutical Research and Early Development  Penzberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Belousov","sequence":"additional","affiliation":[{"name":"Roche Pharmaceutical Research and Early Development, Roche Innovation Centre Basel F. Hoffmann\u2010La Roche Ltd.  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