{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:20:21Z","timestamp":1792153221649,"version":"4.4.0"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2010,9,14]],"date-time":"2010-09-14T00:00:00Z","timestamp":1284422400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0012728","type":"journal-article","created":{"date-parts":[[2010,9,14]],"date-time":"2010-09-14T16:48:54Z","timestamp":1284482934000},"page":"e12728","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":407,"title":["Colonic Biopsies to Assess the Neuropathology of Parkinson's Disease and Its Relationship with Symptoms"],"prefix":"10.1371","volume":"5","author":[{"given":"Thibaud","family":"Lebouvier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Neunlist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislas","family":"Bruley des Varannes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Coron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Drouard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"N'Guyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanguy","family":"Chaumette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Tasselli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Paillusson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathurin","family":"Flamand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Galmiche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Damier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Derkinderen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2010,9,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1365-2982.2008.01094.x","article-title":"The enteric nervous system: normal functions and enteric neuropathies.","volume":"20","author":"JB Furness","year":"2008","journal-title":"Neurogastroenterol Motil"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/j.1365-2982.2004.00538.x","article-title":"Human enteric neuropathies: morphology and molecular pathology.","volume":"16","author":"R De Giorgio","year":"2004","journal-title":"Neurogastroenterol Motil"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/00042737-200504000-00010","article-title":"Cerebellar degeneration and hearing loss in a patient with idiopathic myenteric ganglionitis.","volume":"17","author":"G Basilisco","year":"2005","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.molmed.2004.01.008","article-title":"Brain targeting through the autonomous nervous system: lessons from prion diseases.","volume":"10","author":"S Haik","year":"2004","journal-title":"Trends Mol Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1136\/gut.2005.072447","article-title":"High levels of disease related prion protein in the ileum in variant Creutzfeldt-Jakob disease.","volume":"54","author":"S Joiner","year":"2005","journal-title":"Gut"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1111\/j.1460-9568.2009.06873.x","article-title":"The second brain and Parkinson's disease.","volume":"30","author":"T Lebouvier","year":"2009","journal-title":"Eur J Neurosci"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1016\/S0140-6736(09)60492-X","article-title":"Parkinson's disease.","volume":"373","author":"AJ Lees","year":"2009","journal-title":"Lancet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S1474-4422(06)70373-8","article-title":"Non-motor symptoms of Parkinson's disease: diagnosis and management.","volume":"5","author":"KR Chaudhuri","year":"2006","journal-title":"Lancet Neurol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1002\/mds.21586","article-title":"Prevalence of nonmotor symptoms in Parkinson's disease in an international setting; study using nonmotor symptoms questionnaire in 545 patients.","volume":"22","author":"P Martinez-Martin","year":"2007","journal-title":"Mov Disord"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1001\/archneur.61.12.1906","article-title":"The rate of cognitive decline in Parkinson disease.","volume":"61","author":"D Aarsland","year":"2004","journal-title":"Arch Neurol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1002\/mds.20942","article-title":"Excess burden of constipation in Parkinson's disease: a pilot study.","volume":"21","author":"J Kaye","year":"2006","journal-title":"Mov Disord"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in Lewy bodies.","volume":"388","author":"MG Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/ncb748","article-title":"alpha-Synuclein is phosphorylated in synucleinopathy lesions.","volume":"4","author":"H Fujiwara","year":"2002","journal-title":"Nat Cell Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"29739","DOI":"10.1074\/jbc.M600933200","article-title":"Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease.","volume":"281","author":"JP Anderson","year":"2006","journal-title":"J Biol Chem"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"II3","DOI":"10.1007\/PL00007758","article-title":"Pathoanatomy of Parkinson's disease.","volume":"247","author":"H Braak","year":"2000","journal-title":"J Neurol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/0016-5085(84)90079-9","article-title":"Esophageal Lewy bodies associated with ganglion cell loss in achalasia. Similarity to Parkinson's disease.","volume":"87","author":"SJ Qualman","year":"1984","journal-title":"Gastroenterology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/S1353-8020(09)70769-2","article-title":"Neuropathology of non-motor features of Parkinson disease.","volume":"15","author":"DW Dickson","year":"2009","journal-title":"Parkinsonism Relat Disord"},{"key":"ref18","article-title":"Routine colonic biopsies as a new tool to study the enteric nervous system in living patients.","author":"T Lebouvier","year":"2009","journal-title":"Neurogastroenterol Motil"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1136\/gut.2008.162503","article-title":"Pathological lesions in colonic biopsies during Parkinson's disease.","volume":"57","author":"T Lebouvier","year":"2008","journal-title":"Gut"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1136\/jnnp.55.3.181","article-title":"Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.","volume":"55","author":"AJ Hughes","year":"1992","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref21","first-page":"153","article-title":"Unified Parkinson's disease rating scale.","author":"S Fahn","year":"1987"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1136\/jnnp.2005.062950","article-title":"Mirror movements in parkinsonism: evaluation of a new clinical sign.","volume":"76","author":"AJ Espay","year":"2005","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref23","first-page":"307","article-title":"Guidelines\u2013Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders.","volume":"15","year":"2006","journal-title":"J Gastrointestin Liver Dis"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1001\/archneur.60.4.529","article-title":"Parkinson disease with old-age onset: a comparative study with subjects with middle-age onset.","volume":"60","author":"NJ Diederich","year":"2003","journal-title":"Arch Neurol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.neulet.2005.11.012","article-title":"Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology.","volume":"396","author":"H Braak","year":"2006","journal-title":"Neurosci Lett"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1113\/jphysiol.2003.053140","article-title":"Long vasodilator reflexes projecting through the myenteric plexus in guinea-pig ileum.","volume":"553","author":"DE Reed","year":"2003","journal-title":"J Physiol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/S0140-6736(95)92707-7","article-title":"Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation.","volume":"346","author":"C Singaram","year":"1995","journal-title":"Lancet"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1093\/hmg\/ddq038","article-title":"Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated alpha-synuclein gene mutations precede central nervous system changes.","volume":"19","author":"YM Kuo","year":"2010","journal-title":"Hum Mol Genet"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/cne.10599","article-title":"Chemical coding of the human gastrointestinal nervous system: cholinergic, VIPergic, and catecholaminergic phenotypes.","volume":"459","author":"M Anlauf","year":"2003","journal-title":"J Comp Neurol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1097\/NEN.0b013e318186de48","article-title":"Lewy body pathology involves cutaneous nerves.","volume":"67","author":"M Ikemura","year":"2008","journal-title":"J Neuropathol Exp Neurol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1093\/brain\/awm302","article-title":"Axonal alpha-synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Parkinson's disease.","volume":"131","author":"S Orimo","year":"2008","journal-title":"Brain"},{"key":"ref32","article-title":"Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders.","author":"TG Beach","year":"2010","journal-title":"Acta Neuropathol"},{"key":"ref33","first-page":"41","article-title":"Investigation of general and cytoskeletal markers to estimate numbers and proportions of neurons in the human intestine.","volume":"21","author":"D Ganns","year":"2006","journal-title":"Histol Histopathol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S1474-4422(03)00307-7","article-title":"Gastrointestinal dysfunction in Parkinson's disease.","volume":"2","author":"RF Pfeiffer","year":"2003","journal-title":"Lancet Neurol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1080\/003655299750025327","article-title":"Psychometric validation of a constipation symptom assessment questionnaire.","volume":"34","author":"L Frank","year":"1999","journal-title":"Scand J Gastroenterol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/j.1365-2982.2008.01134.x","article-title":"Enteric neurodegeneration in ageing.","volume":"20","author":"M Camilleri","year":"2008","journal-title":"Neurogastroenterol Motil"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1743-3150.2004.00469.x","article-title":"Neurodegeneration: a key factor in the ageing gut.","volume":"16","author":"PR Wade","year":"2004","journal-title":"Neurogastroenterol Motil"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.neurobiolaging.2006.05.019","article-title":"Age-related neuronal loss in the submucosal plexus of the colon of Fischer 344 rats.","volume":"28","author":"RJ Phillips","year":"2007","journal-title":"Neurobiol Aging"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s00429-006-0123-z","article-title":"Effects of age on sympathetic innervation of the myenteric plexus and gastrointestinal smooth muscle of Fischer 344 rats.","volume":"211","author":"RJ Phillips","year":"2006","journal-title":"Anat Embryol (Berl)"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1053\/gast.2002.36600","article-title":"Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon.","volume":"123","author":"T Wedel","year":"2002","journal-title":"Gastroenterology"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1002\/mds.20996","article-title":"Clinical phenotype of subjects with Parkinson's disease and orthostatic hypotension: autonomic symptom and demographic comparison.","volume":"21","author":"LM Allcock","year":"2006","journal-title":"Mov Disord"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jns.2008.02.017","article-title":"Cardiac sympathetic denervation is correlated with Parkinsonian midline motor symptoms.","volume":"270","author":"JS Kim","year":"2008","journal-title":"J Neurol Sci"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1136\/jnnp.2008.166629","article-title":"Patterns of motor and non-motor features in Parkinson's disease.","volume":"80","author":"SM van Rooden","year":"2009","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1002\/mds.20897","article-title":"Changes in motor subtype and risk for incident dementia in Parkinson's disease.","volume":"21","author":"G Alves","year":"2006","journal-title":"Mov Disord"},{"key":"ref45","article-title":"Routine colonic biopsies as a new tool to study the enteric nervous system in living patients.","author":"T Lebouvier","year":"2009","journal-title":"Neurogastroenterol Motil In press"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1067\/mge.2001.117545","article-title":"Complications of diagnostic and therapeutic colonoscopy within a defined population in Sweden.","volume":"54","author":"G Dafnis","year":"2001","journal-title":"Gastrointest Endosc"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s00401-008-0450-7","article-title":"Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy body disorders.","volume":"117","author":"TG Beach","year":"2009","journal-title":"Acta Neuropathol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.neulet.2009.12.027","article-title":"Clinical availability of skin biopsy in the diagnosis of Parkinson's disease.","volume":"469","author":"Y Miki","year":"2010","journal-title":"Neurosci Lett"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1002\/mds.22464","article-title":"Biopsies of olfactory epithelium in patients with Parkinson's disease.","volume":"24","author":"M Witt","year":"2009","journal-title":"Mov Disord"},{"key":"ref50","article-title":"Biopsable neural tissues: toward new biomarkers for Parkinson's disease?","author":"T Lebouvier","year":"2010","journal-title":"Front Neurosci in press"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1053\/j.gastro.2009.07.005","article-title":"Activation of human enteric neurons by supernatants of colonic biopsy specimens from patients with irritable bowel syndrome.","volume":"137","author":"S Buhner","year":"2009","journal-title":"Gastroenterology"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.1365-2990.2007.00874.x","article-title":"Parkinson's disease: a dual-hit hypothesis.","volume":"33","author":"CH Hawkes","year":"2007","journal-title":"Neuropathol Appl Neurobiol"},{"key":"ref53","article-title":"The second brain: the scientific basis of gut instinct and a groundbreaking new understanding of nervous disorders of the stomach and intestine.","volume":"xvi","author":"MD Gershon","year":"1998"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1212\/01.wnl.0000281999.56102.b5","article-title":"Enteric nervous system: Functional organization and neurologic implications.","volume":"69","author":"EE Benarroch","year":"2007","journal-title":"Neurology"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.autneu.2007.04.005","article-title":"Innervation of the gastrointestinal tract: patterns of aging.","volume":"136","author":"RJ Phillips","year":"2007","journal-title":"Auton Neurosci"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.expneurol.2009.07.025","article-title":"Alpha-synuclein immunopositive aggregates in the myenteric plexus of the aging Fischer 344 rat.","volume":"220","author":"RJ Phillips","year":"2009","journal-title":"Exp Neurol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0012728","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,4]],"date-time":"2019-06-04T15:30:27Z","timestamp":1559662227000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0012728"}},"subtitle":[],"editor":[{"given":"Mark R.","family":"Cookson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2010,9,14]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2010,9,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0012728","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.5558957.5526056","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,14]]}}}