{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:15:44Z","timestamp":1791224144294,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,12,18]],"date-time":"2013-12-18T00:00:00Z","timestamp":1387324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Parkinson's disease is characterized by the pathological aggregation of Alpha\u2010synuclein. The dual\u2010hit hypothesis proposed by Braak implicates the enteric nervous system as an initial site of \u03b1\u2010synuclein aggregation with subsequent spread to the central nervous system. Regional variations in the spatial pattern or levels of \u03b1\u2010synuclein along the enteric nervous system could have implications for identifying sites of onset of this pathogenic cascade. We performed immunohistochemical staining for \u03b1\u2010synuclein on gastrointestinal tissue from patients with no history of neurological disease using the established LB509 antibody and a new clone, MJFR1, characterized for immunohistochemistry here. We demonstrate that the vermiform appendix is particularly enriched in \u03b1\u2010synuclein\u2013containing axonal varicosities, concentrated in its mucosal plexus rather than the classical submucosal and myenteric plexuses. Unexpectedly, intralysosomal accumulations of \u03b1\u2010synuclein were detected within mucosal macrophages of the appendix. The abundance and accumulation of \u03b1\u2010synuclein in the vermiform appendix implicate it as a candidate anatomical locus for the initiation of enteric \u03b1\u2010synuclein aggregation and permits the generation of testable hypotheses for Parkinson's disease pathogenesis. \u00a9 2013 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.25779","type":"journal-article","created":{"date-parts":[[2013,12,18]],"date-time":"2013-12-18T14:00:41Z","timestamp":1387375241000},"page":"991-998","source":"Crossref","is-referenced-by-count":121,"title":["Alpha\u2010synuclein in the appendiceal mucosa of neurologically intact subjects"],"prefix":"10.1002","volume":"29","author":[{"given":"Madison T.","family":"Gray","sequence":"first","affiliation":[{"name":"Centre for Cancer Therapeutics Ottawa Hospital Research Institute Ottawa Ontario Canada"},{"name":"Department of Pathology and Laboratory Medicine Faculty of Medicine University of Ottawa Ottawa Ontario Canada"},{"name":"Department of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Munoz","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Gray","sequence":"additional","affiliation":[{"name":"Centre for Cancer Therapeutics Ottawa Hospital Research Institute Ottawa Ontario Canada"},{"name":"Department of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Schlossmacher","sequence":"additional","affiliation":[{"name":"Division of Neuroscience Ottawa Hospital Research Institute Ottawa Ontario Canada"},{"name":"Division of Neurology The Ottawa Hospital Ottawa Ontario Canada"},{"name":"Department of Medicine Faculty of Medicine University of Ottawa Ottawa Ontario Canada"},{"name":"Department of Cellular and Molecular Medicine Faculty of Medicine University of Ottawa Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Woulfe","sequence":"additional","affiliation":[{"name":"Centre for Cancer Therapeutics Ottawa Hospital Research Institute Ottawa Ontario Canada"},{"name":"Department of Pathology and Laboratory Medicine Faculty of Medicine University of Ottawa Ottawa Ontario Canada"},{"name":"Department of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa Ottawa Ontario Canada"},{"name":"Department of Pathology and Laboratory Medicine The Ottawa Hospital Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,12,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0711-0"},{"key":"e_1_2_8_3_1","first-page":"920","article-title":"Paralysis agitans. I. Pathologische Anatomy","author":"Lewy FH","year":"1912","journal-title":"Handbuch der Neurologie"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.67"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43366"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1746"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227157"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008762"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00898"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s004010000247","article-title":"alpha\u2010synuclein immunopositive Parkinson's disease\u2010related inclusion bodies in lower brain stem nuclei","volume":"101","author":"Braak E","year":"2001","journal-title":"Acta Neuropathol"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.5.413"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-002-0808-2"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-004-0956-9"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.09.030"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.06.003"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2007.00874.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903040209"},{"issue":"1","key":"e_1_2_8_19_1","first-page":"R200","article-title":"Topography of efferent vagal innervation of the rat gastrointestinal tract","volume":"260","author":"Berthoud HR","year":"1991","journal-title":"Am J Physiol"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903010107"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2006.06.004"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.1998.19220257.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1439-0264.2002.00403.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(80)90067-6"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-011-0807-1"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215549904700601"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-007-7216-x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4564-06.2007"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23838"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25298"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00687767"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0664-3"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-009-0657-2"},{"key":"e_1_2_8_34_1","unstructured":"DraschO.Contributions to the knowledge of the fine structure of the small intestine especially on the nerves thereof1881;82:168\u2010198. [German]"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(83)90072-0"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.02.074"},{"key":"e_1_2_8_37_1","first-page":"1","volume-title":"Structure of the enteric nervous system. The Enteric Nervous System. Malden","author":"Furness JB","year":"2006"},{"key":"e_1_2_8_38_1","first-page":"1053","article-title":"Ultrastructural localization of the CD68 macrophage\u2010associated antigen in human blood neutrophils and monocytes","volume":"139","author":"Saito N","year":"1991","journal-title":"Am J Pathol"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1992.tb00351.x"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1998.00557.x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2012.02.004"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e3283503e4f"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1560-11.2011"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03514-X"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-011-0653-2"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1247477"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.25779","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.25779","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.25779","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:36:12Z","timestamp":1760956572000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.25779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,18]]},"references-count":45,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1002\/mds.25779"],"URL":"https:\/\/doi.org\/10.1002\/mds.25779","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,18]]}}}