{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:18:26Z","timestamp":1790360306696,"version":"4.1.0"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder caused by the conformational conversion of the prion protein (PrP<jats:sup>C<\/jats:sup>) into an abnormally folded form, named prion (or PrP<jats:sup>Sc<\/jats:sup>). The combination of the polymorphism at codon 129 of the PrP gene (coding either methionine or valine) with the biochemical feature of the proteinase-K resistant PrP (generating either PrP<jats:sup>Sc<\/jats:sup> type 1 or 2) gives rise to different PrP<jats:sup>Sc<\/jats:sup> strains, which cause variable phenotypes of sCJD. The definitive diagnosis of sCJD and its classification can be achieved only post-mortem after PrP<jats:sup>Sc<\/jats:sup> identification and characterization in the brain. By exploiting the Real-Time Quaking-Induced Conversion (RT-QuIC) assay, traces of PrP<jats:sup>Sc<\/jats:sup> were found in the olfactory mucosa (OM) of sCJD patients, thus demonstrating that PrP<jats:sup>Sc<\/jats:sup> is not confined to the brain. Here, we have optimized another technique, named protein misfolding cyclic amplification (PMCA) for detecting PrP<jats:sup>Sc<\/jats:sup> in OM samples of sCJD patients. OM samples were collected from 27 sCJD and 2 genetic CJD patients (E200K). Samples from 34 patients with other neurodegenerative disorders were included as controls. Brains were collected from 26 sCJD patients and 16 of them underwent OM collection. Brain and OM samples were subjected to PMCA using the brains of transgenic mice expressing human PrP<jats:sup>C<\/jats:sup> with methionine at codon 129 as reaction substrates. The amplified products were analyzed by Western blot after proteinase K digestion. Quantitative PMCA was performed to estimate PrP<jats:sup>Sc<\/jats:sup> concentration in OM. PMCA enabled the detection of prions in OM samples with 79.3% sensitivity and 100% specificity. Except for a few cases, a predominant type 1 PrP<jats:sup>Sc<\/jats:sup> was generated, regardless of the tissues analyzed. Notably, all amplified PrP<jats:sup>Sc<\/jats:sup> were less resistant to PK compared to the original strain. In conclusion, although the optimized PMCA did not consent to recognize sCJD subtypes from the analysis of OM collected from living patients, it enabled us to estimate for the first time the amount of prions accumulating in this biological tissue. Further assay optimizations are needed to faithfully amplify peripheral prions whose recognition could lead to a better diagnosis and selection of patients for future clinical trials.<\/jats:p>","DOI":"10.3389\/fnagi.2022.848991","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T17:05:03Z","timestamp":1648573503000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["PMCA-Based Detection of Prions in the Olfactory Mucosa of Patients With Sporadic Creutzfeldt\u2013Jakob Disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Federico Angelo","family":"Cazzaniga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Bistaffa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Maria Giulia","family":"De Luca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Maria","family":"Portaleone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Catania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Redaelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Tramacere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Bufano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Caroppo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Giovagnoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Tiraboschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Di Fede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Eleopra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Devigili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Emanuele","family":"Elia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Cilia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Fiorini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Bongianni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Salzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Celauro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico Giuseppe","family":"Quarta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Mammana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Legname","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Tagliavini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Parchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Zanusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Giaccone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Moda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1136\/jnnp-2013-307035","article-title":"Validation of the new consensus criteria for the diagnosis of corticobasal degeneration.","volume":"85","author":"Alexander","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"8462","DOI":"10.1128\/jvi.77.15.8462-8469.2003","article-title":"Evaluation of quinacrine treatment for prion diseases.","volume":"77","author":"Barret","year":"2003","journal-title":"J. Virol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1002\/cjp2.90","article-title":"Rapid amplification of prions from variant Creutzfeldt-Jakob disease cerebrospinal fluid.","volume":"4","author":"Barria","year":"2018","journal-title":"J. Pathol. Clin. Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"169","DOI":"10.4161\/pri.27836","article-title":"The many shades of prion strain adaptation.","volume":"8","author":"Baskakov","year":"2014","journal-title":"Prion"},{"key":"B5","doi-asserted-by":"publisher","first-page":"17093","DOI":"10.1074\/jbc.M116.731117","article-title":"Sialic acid within the glycosylphosphatidylinositol anchor targets the cellular prion protein to synapses.","volume":"291","author":"Bate","year":"2016","journal-title":"J. Biol. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"4058","DOI":"10.1038\/s41598-021-83630-1","article-title":"Sensitive protein misfolding cyclic amplification of sporadic Creutzfeldt-Jakob disease prions is strongly seed and substrate dependent.","volume":"11","author":"B\u00e9londrade","year":"2021","journal-title":"Sci. Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"E4160","DOI":"10.1073\/pnas.1317164110","article-title":"Drug resistance confounding prion therapeutics.","volume":"110","author":"Berry","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s00401-017-1670-5","article-title":"Prion disease: experimental models and reality.","volume":"133","author":"Brandner","year":"2017","journal-title":"Acta Neuropathol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/39057","article-title":"Transmissions to mice indicate that \u201cnew variant\u201d CJD is caused by the BSE agent.","volume":"389","author":"Bruce","year":"1997","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"5191","DOI":"10.1038\/s41598-019-41694-0","article-title":"PMCA-replicated PrPD in urine of vCJD patients maintains infectivity and strain characteristics of brain PrPD: transmission study.","volume":"9","author":"Cali","year":"2019","journal-title":"Sci. Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1038\/s41598-020-58446-0","article-title":"Co-existence of PrPD types 1 and 2 in sporadic Creutzfeldt-Jakob disease of the VV subgroup: phenotypic and prion protein characteristics.","volume":"10","author":"Cali","year":"2020","journal-title":"Sci. Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1038\/s41374-019-0282-1","article-title":"Role of prion protein glycosylation in replication of human prions by protein misfolding cyclic amplification.","volume":"99","author":"Camacho","year":"2019","journal-title":"Lab. Invest."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e00393-20","DOI":"10.1128\/mBio.00393-20","article-title":"Prions from sporadic creutzfeldt-jakob disease patients propagate as strain mixtures.","volume":"11","author":"Cassard","year":"2020","journal-title":"mBio"},{"key":"B14","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/s0968-0004(01)01792-3","article-title":"Interactions between prion protein isoforms: the kiss of death?","volume":"26","author":"Caughey","year":"2001","journal-title":"Trends Biochem. Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nmeth.1465","article-title":"Estimating prion concentration in fluids and tissues by quantitative PMCA.","volume":"7","author":"Chen","year":"2010","journal-title":"Nat. Methods"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1136\/jnnp.55.11.1094","article-title":"Creutzfeldt-Jakob disease in a recipient of human pituitary-derived gonadotrophin: a second case.","volume":"55","author":"Cochius","year":"1992","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1126\/science.1190815","article-title":"Prion strain mutation and selection.","volume":"328","author":"Collinge","year":"2010","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"370ra183","DOI":"10.1126\/scitranslmed.aaf6188","article-title":"Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease.","volume":"8","author":"Concha-Marambio","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"13794","DOI":"10.1128\/JVI.01502-07","article-title":"Prion strain- and species-dependent effects of antiprion molecules in primary neuronal cultures.","volume":"81","author":"Cronier","year":"2007","journal-title":"J. Virol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1111\/vox.12161","article-title":"Variant CJD and blood transfusion: are there additional cases?","volume":"107","author":"Davidson","year":"2014","journal-title":"Vox Sang."},{"key":"B21","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s40035-019-0164-x","article-title":"Efficient RT-QuIC seeding activity for \u03b1-synuclein in olfactory mucosa samples of patients with Parkinson\u2019s disease and multiple system atrophy.","volume":"8","author":"De Luca","year":"2019","journal-title":"Transl. Neurodegener."},{"key":"B22","doi-asserted-by":"publisher","first-page":"4280","DOI":"10.1007\/s12035-021-02418-6","article-title":"Decrease in skin prion-seeding activity of prion-infected mice treated with a compound against human and animal prions: a first possible biomarker for prion therapeutics.","volume":"58","author":"Ding","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s00106-002-0651-7","article-title":"Diagnosis of prion diseases.","volume":"50","author":"Federspil","year":"2002","journal-title":"HNO"},{"key":"B24","doi-asserted-by":"publisher","first-page":"10655","DOI":"10.1038\/s41598-017-10922-w","article-title":"High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions.","volume":"7","author":"Franceschini","year":"2017","journal-title":"Sci. Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1002\/ana.21420","article-title":"A novel human disease with abnormal prion protein sensitive to protease.","volume":"63","author":"Gambetti","year":"2008","journal-title":"Ann. Neurol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1212\/01.wnl.0000324625.00404.15","article-title":"Second consensus statement on the diagnosis of multiple system atrophy.","volume":"71","author":"Gilman","year":"2008","journal-title":"Neurology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1111\/j.1440-1789.2009.01023.x","article-title":"The risk of iatrogenic Creutzfeldt-Jakob disease through medical and surgical procedures.","volume":"29","author":"Hamaguchi","year":"2009","journal-title":"Neuropathology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1136\/jnnp.2005.073395","article-title":"Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK.","volume":"77","author":"Heath","year":"2006","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B29","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1136\/jnnp.63.3.388","article-title":"Transmission of Creutzfeldt-Jakob disease via a corneal transplant.","volume":"63","author":"Heckmann","year":"1997","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B30","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S1474-4422(20)30477-4","article-title":"Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease.","volume":"20","author":"Hermann","year":"2021","journal-title":"Lancet Neurol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/38925","article-title":"The same prion strain causes vCJD and BSE.","volume":"389","author":"Hill","year":"1997","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1002\/mds.26987","article-title":"Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria.","volume":"32","author":"H\u00f6glinger","year":"2017","journal-title":"Mov. Disord."},{"key":"B33","doi-asserted-by":"publisher","first-page":"28515","DOI":"10.1074\/jbc.M313762200","article-title":"The residue 129 polymorphism in human prion protein does not confer susceptibility to Creutzfeldt-Jakob disease by altering the structure or global stability of PrPC.","volume":"279","author":"Hosszu","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1017\/CBO9781107588660.010","article-title":"Human prion diseases","author":"Ironside","year":"2014","journal-title":"Neuropathology of Neurodegenerative Diseases"},{"key":"B35","year":"","journal-title":"Istituto Superiore di Sanit\u00e0 Criteri Diagnostici per le Encefalopatie Spongiformi Trasmissibili Umane-Criteri per la Sorveglianza."},{"key":"B36","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1111\/j.1537-2995.2008.01954.x","article-title":"Human platelets as a substrate source for the in vitro amplification of the abnormal prion protein (PrP) associated with variant Creutzfeldt-Jakob disease.","volume":"49","author":"Jones","year":"2009","journal-title":"Transfusion"},{"key":"B37","doi-asserted-by":"publisher","first-page":"111","DOI":"10.4161\/pri.27661","article-title":"Implications of prion adaptation and evolution paradigm for human neurodegenerative diseases.","volume":"8","author":"Kabir","year":"2014","journal-title":"Prion"},{"key":"B38","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/2051-5960-1-74","article-title":"Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M\/V and type 2 abnormal prion protein.","volume":"1","author":"Kobayashi","year":"2013","journal-title":"Acta Neuropathol. Commun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s00401-015-1447-7","article-title":"The influence of PRNP polymorphisms on human prion disease susceptibility: an update.","volume":"130","author":"Kobayashi","year":"2015","journal-title":"Acta Neuropathol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1093\/bmb\/66.1.267","article-title":"Diagnosis of prion diseases.","volume":"66","author":"K\u00fcbler","year":"2003","journal-title":"Br. Med. Bull."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1212\/01.WNL.0000160117.56690.B2","article-title":"Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada.","volume":"64","author":"Ladogana","year":"2005","journal-title":"Neurology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1126\/science.1183218","article-title":"Darwinian evolution of prions in cell culture.","volume":"327","author":"Li","year":"2010","journal-title":"Science"},{"key":"B43","doi-asserted-by":"publisher","first-page":"252","DOI":"10.4161\/pri.19930","article-title":"Genesis of tramsmissible protein states via deformed templating.","volume":"6","author":"Makarava","year":"2012","journal-title":"Prion"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e1003759","DOI":"10.1371\/journal.ppat.1003759","article-title":"The evolution of transmissible prions: the role of deformed templating.","volume":"9","author":"Makarava","year":"2013","journal-title":"PLoS Pathog."},{"key":"B45","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1002\/acn3.51000","article-title":"Detection of prions in skin punch biopsies of Creutzfeldt-Jakob disease patients.","volume":"7","author":"Mammana","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease.","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2310","DOI":"10.1073\/pnas.83.8.2310","article-title":"Separation and properties of cellular and scrapie prion proteins.","volume":"83","author":"Meyer","year":"1986","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B48","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1056\/NEJMoa1404401","article-title":"Prions in the urine of patients with variant Creutzfeldt-Jakob disease.","volume":"371","author":"Moda","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"20526","DOI":"10.1038\/srep20526","article-title":"Strain-dependent profile of misfolded prion protein aggregates.","volume":"6","author":"Morales","year":"2016","journal-title":"Sci. Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1038\/labinvest.3700676","article-title":"A refined method for molecular typing reveals that co-occurrence of PrP(Sc) types in Creutzfeldt-Jakob disease is not the rule.","volume":"87","author":"Notari","year":"2007","journal-title":"Lab. Invest."},{"key":"B51","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/0092-8674(85)90333-2","article-title":"A cellular gene encodes scrapie PrP 27-30 protein.","volume":"40","author":"Oesch","year":"1985","journal-title":"Cell"},{"key":"B52","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1056\/NEJMoa1315200","article-title":"A test for Creutzfeldt-Jakob disease using nasal brushings.","volume":"371","author":"Orr\u00fa","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"eaam7785","DOI":"10.1126\/scitranslmed.aam7785","article-title":"Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease.","volume":"9","author":"Orr\u00fa","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"10962","DOI":"10.1073\/pnas.90.23.10962","article-title":"Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.","volume":"90","author":"Pan","year":"1993","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B55","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1002\/ana.410390613","article-title":"Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease.","volume":"39","author":"Parchi","year":"1996","journal-title":"Ann. Neurol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s00401-012-1002-8","article-title":"Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter-rater study among surveillance centres in Europe and USA.","volume":"124","author":"Parchi","year":"2012","journal-title":"Acta Neuropathol."},{"key":"B57","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W","article-title":"Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects.","volume":"46","author":"Parchi","year":"1999","journal-title":"Ann. Neurol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/s00401-009-0585-1","article-title":"Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification.","volume":"118","author":"Parchi","year":"2009","journal-title":"Acta Neuropathol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/S1474-4422(05)70225-8","article-title":"Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob disease.","volume":"4","author":"Polymenidou","year":"2005","journal-title":"Lancet Neurol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS clinical diagnostic criteria for Parkinson\u2019s disease.","volume":"30","author":"Postuma","year":"2015","journal-title":"Mov. Disord."},{"key":"B61","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1126\/science.6801762","article-title":"Novel proteinaceous infectious particles cause scrapie.","volume":"216","author":"Prusiner","year":"1982","journal-title":"Science"},{"key":"B62","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1016\/S1474-4422(12)70063-7","article-title":"Sporadic human prion diseases: molecular insights and diagnosis.","volume":"11","author":"Puoti","year":"2012","journal-title":"Lancet Neurol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1212\/wnl.53.9.2173","article-title":"Sporadic Creutzfeldt-Jakob disease: co-occurrence of different types of PrP(Sc) in the same brain.","volume":"53","author":"Puoti","year":"1999","journal-title":"Neurology"},{"key":"B64","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1093\/brain\/awr179","article-title":"Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia.","volume":"134","author":"Rascovsky","year":"2011","journal-title":"Brain"},{"key":"B65","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1002\/acn3.51057","article-title":"Transmission of CJD from nasal brushings but not spinal fluid or RT-QuIC product.","volume":"7","author":"Raymond","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"46269","DOI":"10.1038\/srep46269","article-title":"Detection of prion seeding activity in the olfactory mucosa of patients with Fatal Familial Insomnia.","volume":"7","author":"Redaelli","year":"2017","journal-title":"Sci. Rep."},{"key":"B67","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/bs.pmbts.2017.06.011","article-title":"Neuropathology of human prion diseases.","volume":"150","author":"Ritchie","year":"2017","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"309","DOI":"10.3390\/v11040309","article-title":"Understanding prion strains: evidence from studies of the disease forms affecting humans.","volume":"11","author":"Rossi","year":"2019","journal-title":"Viruses"},{"key":"B69","doi-asserted-by":"publisher","first-page":"13044","DOI":"10.1073\/pnas.96.23.13044","article-title":"Glycosylation differences between the normal and pathogenic prion protein isoforms.","volume":"96","author":"Rudd","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B70","doi-asserted-by":"publisher","first-page":"108","DOI":"10.4161\/pri.18666","article-title":"Molecular pathogenesis of sporadic prion diseases in man.","volume":"6","author":"Safar","year":"2012","journal-title":"Prion"},{"key":"B71","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/0092-8674(87)90150-4","article-title":"Scrapie prion protein contains a phosphatidylinositol glycolipid.","volume":"51","author":"Stahl","year":"1987","journal-title":"Cell"},{"key":"B72","doi-asserted-by":"publisher","first-page":"31390","DOI":"10.1074\/jbc.M401754200","article-title":"Methionine 129 variant of human prion protein oligomerizes more rapidly than the valine 129 variant: implications for disease susceptibility to Creutzfeldt-Jakob disease.","volume":"279","author":"Tahiri-Alaoui","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B73","doi-asserted-by":"publisher","first-page":"9936","DOI":"10.1073\/pnas.91.21.9936","article-title":"Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein.","volume":"91","author":"Telling","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B74","doi-asserted-by":"publisher","first-page":"e1000029","DOI":"10.1371\/journal.ppat.1000029","article-title":"Beyond PrP res type 1\/type 2 dichotomy in Creutzfeldt-Jakob disease.","volume":"4","author":"Uro-Coste","year":"2008","journal-title":"PLoS Pathog."},{"key":"B75","doi-asserted-by":"publisher","first-page":"e2146319","DOI":"10.1001\/jamanetworkopen.2021.46319","article-title":"Validation of revised international creutzfeldt-jakob disease surveillance network diagnostic criteria for sporadic Creutzfeldt-Jakob disease.","volume":"5","author":"Watson","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"B76","year":"2003","journal-title":"WHO Manual for Surveillance of Human Transmissible Spongiform Encephalopathies Including Variant Creutzfeldt-Jakob Disease."},{"key":"B77","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.neulet.2011.04.072","article-title":"Heparin enhances the cell-protein misfolding cyclic amplification efficiency of variant Creutzfeldt-Jakob disease.","volume":"498","author":"Yokoyama","year":"2011","journal-title":"Neurosci. Lett."},{"key":"B78","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/1471-2334-4-53","article-title":"Pharmacokinetics of quinacrine in the treatment of prion disease.","volume":"4","author":"Yung","year":"2004","journal-title":"BMC Infect. Dis."},{"key":"B79","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1056\/NEJMoa022043","article-title":"Detection of pathologic prion protein in the olfactory epithelium in sporadic Creutzfeldt-Jakob disease.","volume":"348","author":"Zanusso","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"B80","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/B978-0-444-63945-5.00009-X","article-title":"Sporadic Creutzfeldt-Jakob disease.","volume":"153","author":"Zerr","year":"2018","journal-title":"Handb. Clin. Neurol."}],"updated-by":[{"DOI":"10.3389\/fnagi.2023.1073356","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000}}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.848991\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T14:56:24Z","timestamp":1677509784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.848991\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,25]]},"references-count":80,"alternative-id":["10.3389\/fnagi.2022.848991"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.848991","relation":{"corrigendum":[{"id-type":"doi","id":"10.3389\/fnagi.2023.1073356","asserted-by":"object"}]},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,25]]},"article-number":"848991"}}