{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:40:45Z","timestamp":1791999645769,"version":"4.4.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,10,25]],"date-time":"2010-10-25T00:00:00Z","timestamp":1287964800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrP<jats:sup>Sc<\/jats:sup>) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed \"protease-sensitive prionopathy\", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case presentation<\/jats:title>\n            <jats:p>We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of \"protease-sensitive prionopathy\". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen\/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrP<jats:sup>Sc<\/jats:sup> showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrP<jats:sup>Sc<\/jats:sup> was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine\/valine.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the \"protease-sensitive prionopathy\". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2377-10-99","type":"journal-article","created":{"date-parts":[[2010,10,26]],"date-time":"2010-10-26T06:15:35Z","timestamp":1288073735000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine\/valine at codon 129: Case report"],"prefix":"10.1186","volume":"10","author":[{"given":"Ana B","family":"Rodr\u00edguez-Mart\u00ednez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseba M","family":"Garrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J","family":"Zarranz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M","family":"Arteagoitia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian M","family":"de Pancorbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Atar\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miren J","family":"Bilbao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidro","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n A","family":"Juste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,10,25]]},"reference":[{"key":"380_CR1","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1212\/01.WNL.0000160117.56690.B2","volume":"64","author":"A Ladogana","year":"2005","unstructured":"Ladogana A, Puopolo M, Croes EA, Budka H, Jarius C, Collins S, Klug GM, Sutcliffe T, Giulivi A, Alperovitch A, et al: Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada. Neurology. 2005, 64: 1586-1591. 10.1212\/01.WNL.0000160117.56690.B2.","journal-title":"Neurology"},{"key":"380_CR2","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W","volume":"46","author":"P Parchi","year":"1999","unstructured":"Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, et al: Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol. 1999, 46: 224-233. 10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W.","journal-title":"Ann Neurol"},{"key":"380_CR3","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1111\/j.1365-2990.2005.00697.x","volume":"31","author":"JW Ironside","year":"2005","unstructured":"Ironside JW, Ritchie DL, Head MW: Phenotypic variability in human prion diseases. Neuropathol Appl Neurobiol. 2005, 31: 565-579. 10.1111\/j.1365-2990.2005.00697.x.","journal-title":"Neuropathol Appl Neurobiol"},{"key":"380_CR4","first-page":"135","volume":"16","author":"H Budka","year":"2000","unstructured":"Budka H: Histopathology and immunohistochemistry of human transmissible spongiform encephalopathies (TSEs). Arch Virol Suppl. 2000, 16: 135-142.","journal-title":"Arch Virol Suppl"},{"key":"380_CR5","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1111\/j.1750-3639.1996.tb00869.x","volume":"6","author":"JW Ironside","year":"1996","unstructured":"Ironside JW: Review: Creutzfeldt-Jakob disease. Brain Pathol. 1996, 6: 379-388. 10.1111\/j.1750-3639.1996.tb00869.x.","journal-title":"Brain Pathol"},{"key":"380_CR6","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1002\/ana.410390613","volume":"39","author":"P Parchi","year":"1996","unstructured":"Parchi P, Castellani R, Capellari S, Ghetti B, Young K, Chen SG, Farlow M, Dickson DW, Sima AA, Trojanowski JQ, et al: Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol. 1996, 39: 767-778. 10.1002\/ana.410390613.","journal-title":"Ann Neurol"},{"key":"380_CR7","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1136\/jnnp.2007.115444","volume":"78","author":"G Giaccone","year":"2007","unstructured":"Giaccone G, Di Fede G, Mangieri M, Limido L, Capobianco R, Suardi S, Grisoli M, Binelli S, Fociani P, Bugiani O, et al: A novel phenotype of sporadic Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry. 2007, 78: 1379-1382. 10.1136\/jnnp.2007.115444.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"380_CR8","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1001\/archneur.64.4.595","volume":"64","author":"G Zanusso","year":"2007","unstructured":"Zanusso G, Polo A, Farinazzo A, Nonno R, Cardone F, Di Bari M, Ferrari S, Principe S, Gelati M, Fasoli E, et al: Novel prion protein conformation and glycotype in Creutzfeldt-Jakob disease. Arch Neurol. 2007, 64: 595-599. 10.1001\/archneur.64.4.595.","journal-title":"Arch Neurol"},{"key":"380_CR9","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s00401-007-0242-5","volume":"114","author":"B Krebs","year":"2007","unstructured":"Krebs B, Bader B, Klehmet J, Grasbon-Frodl E, Oertel WH, Zerr I, Stricker S, Zschenderlein R, Kretzschmar HA: A novel subtype of Creutzfeldt-Jakob disease characterized by a small 6 kDa PrP fragment. Acta Neuropathol. 2007, 114: 195-199. 10.1007\/s00401-007-0242-5.","journal-title":"Acta Neuropathol"},{"key":"380_CR10","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1002\/ana.21420","volume":"63","author":"P Gambetti","year":"2008","unstructured":"Gambetti P, Dong Z, Yuan J, Xiao X, Zheng M, Alshekhlee A, Castellani R, Cohen M, Barria MA, Gonzalez-Romero D, et al: A novel human disease with abnormal prion protein sensitive to protease. Ann Neurol. 2008, 63: 697-708. 10.1002\/ana.21420.","journal-title":"Ann Neurol"},{"key":"380_CR11","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1093\/bmb\/66.1.213","volume":"66","author":"P Gambetti","year":"2003","unstructured":"Gambetti P, Kong Q, Zou W, Parchi P, Chen SG: Sporadic and familial CJD: classification and characterisation. Br Med Bull. 2003, 66: 213-239. 10.1093\/bmb\/66.1.213.","journal-title":"Br Med Bull"},{"key":"380_CR12","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/s00401-009-0585-1","volume":"118","author":"P Parchi","year":"2009","unstructured":"Parchi P, Strammiello R, Notari S, Giese A, Langeveld JP, Ladogana A, Zerr I, Roncaroli F, Cras P, Ghetti B, et al: Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification. Acta Neuropathol. 2009, 118: 659-671. 10.1007\/s00401-009-0585-1.","journal-title":"Acta Neuropathol"},{"key":"380_CR13","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1097\/00005072-199611000-00007","volume":"55","author":"P Piccardo","year":"1996","unstructured":"Piccardo P, Seiler C, Dlouhy SR, Young K, Farlow MR, Prelli F, Frangione B, Bugiani O, Tagliavini F, Ghetti B: Proteinase-K-resistant prion protein isoforms in Gerstmann-Straussler-Scheinker disease (Indiana kindred). J Neuropathol Exp Neurol. 1996, 55: 1157-1163. 10.1097\/00005072-199611000-00007.","journal-title":"J Neuropathol Exp Neurol"},{"key":"380_CR14","doi-asserted-by":"publisher","first-page":"8322","DOI":"10.1073\/pnas.95.14.8322","volume":"95","author":"P Parchi","year":"1998","unstructured":"Parchi P, Chen SG, Brown P, Zou W, Capellari S, Budka H, Hainfellner J, Reyes PF, Golden GT, Hauw JJ, et al: Different patterns of truncated prion protein fragments correlate with distinct phenotypes in P102L Gerstmann-Straussler-Scheinker disease. Proc Natl Acad Sci USA. 1998, 95: 8322-8327. 10.1073\/pnas.95.14.8322.","journal-title":"Proc Natl Acad Sci USA"},{"key":"380_CR15","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1051\/vetres:2007056","volume":"39","author":"SL Benestad","year":"2008","unstructured":"Benestad SL, Arsac JN, Goldmann W, Noremark M: Atypical\/Nor98 scrapie: properties of the agent, genetics, and epidemiology. Vet Res. 2008, 39: 19-10.1051\/vetres:2007056.","journal-title":"Vet Res"},{"key":"380_CR16","first-page":"554","volume":"68","author":"P Gambetti","year":"2009","unstructured":"Gambetti P, Puoti G, Kong Q, Zou W, Tagliavini F, Parchi P: Novel human prion disease affecting 3 prion codon 129 genotypes: the sporadic form of Gerstmann-St\u00e4ussler-Scheinker disease? [abstract]. J Neuropathol Exp Neurol. 2009, 68: 554-","journal-title":"J Neuropathol Exp Neurol"},{"key":"380_CR17","first-page":"45","volume-title":"Prion2009 book of abstracts","author":"P Gambetti","year":"2009","unstructured":"Gambetti P: A novel human prion disease affecting subjects with the three prion protein codon 129 genotypes: could it be the sporadic form of Gerstmann-Str\u00e4ussler? [abstract]. Prion2009 book of abstracts. 2009, 45-"},{"key":"380_CR18","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1126\/science.1439789","volume":"258","author":"LG Goldfarb","year":"1992","unstructured":"Goldfarb LG, Petersen RB, Tabaton M, Brown P, LeBlanc AC, Montagna P, Cortelli P, Julien J, Vital C, Pendelbury WW, et al: Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. Science. 1992, 258: 806-808. 10.1126\/science.1439789.","journal-title":"Science"},{"key":"380_CR19","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1002\/ana.20327","volume":"56","author":"S Haik","year":"2004","unstructured":"Haik S, Peoc'h K, Brandel JP, Privat N, Laplanche JL, Faucheux BA, Hauw JJ: Striking PrPsc heterogeneity in inherited prion diseases with the D178N mutation. Ann Neurol. 2004, 56: 909-910. 10.1002\/ana.20327.","journal-title":"Ann Neurol"},{"key":"380_CR20","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.1093\/brain\/awl224","volume":"129","author":"I Cali","year":"2006","unstructured":"Cali I, Castellani R, Yuan J, Al Shekhlee A, Cohen ML, Xiao X, Moleres FJ, Parchi P, Zou WQ, Gambetti P: Classification of sporadic Creutzfeldt-Jakob disease revisited. Brain. 2006, 129: 2266-2277. 10.1093\/brain\/awl224.","journal-title":"Brain"},{"key":"380_CR21","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1093\/brain\/awl013","volume":"129","author":"AF Hill","year":"2006","unstructured":"Hill AF, Joiner S, Beck JA, Campbell TA, Dickinson A, Poulter M, Wadsworth JD, Collinge J: Distinct glycoform ratios of protease resistant prion protein associated with PRNP point mutations. Brain. 2006, 129: 676-685. 10.1093\/brain\/awl013.","journal-title":"Brain"},{"key":"380_CR22","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s004010051106","volume":"98","author":"O Schaller","year":"1999","unstructured":"Schaller O, Fatzer R, Stack M, Clark J, Cooley W, Biffiger K, Egli S, Doherr M, Vandevelde M, Heim D, et al: Validation of a western immunoblotting procedure for bovine PrP(Sc) detection and its use as a rapid surveillance method for the diagnosis of bovine spongiform encephalopathy (BSE). Acta Neuropathol (Berl). 1999, 98: 437-443. 10.1007\/s004010051106.","journal-title":"Acta Neuropathol (Berl)"},{"key":"380_CR23","doi-asserted-by":"publisher","first-page":"2839","DOI":"10.1073\/pnas.91.7.2839","volume":"91","author":"L Monari","year":"1994","unstructured":"Monari L, Chen SG, Brown P, Parchi P, Petersen RB, Mikol J, Gray F, Cortelli P, Montagna P, Ghetti B, et al: Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism. Proc Natl Acad Sci USA. 1994, 91: 2839-2842. 10.1073\/pnas.91.7.2839.","journal-title":"Proc Natl Acad Sci USA"},{"key":"380_CR24","volume-title":"Instruction Manual for Bovine Spongiform Encephalopathy-Scrapie Antigen test kit","author":"IDEXX Laboratories","year":"2007","unstructured":"IDEXX Laboratories: Instruction Manual for Bovine Spongiform Encephalopathy-Scrapie Antigen test kit. 2007"}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2377-10-99.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2377-10-99\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2377-10-99","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2377-10-99.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T05:31:09Z","timestamp":1630474269000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/1471-2377-10-99"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,25]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["380"],"URL":"https:\/\/doi.org\/10.1186\/1471-2377-10-99","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10,25]]},"assertion":[{"value":"2 October 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"99"}}