{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:26:27Z","timestamp":1788351987959,"version":"build-2803163510"},"reference-count":119,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Prion diseases are neurodegenerative and invariably fatal conditions that affect humans and animals. In particular, Creutzfeldt-Jakob disease (CJD) and bovine spongiform encephalopathy (BSE) are paradigmatic forms of human and animal prion diseases, respectively. Human exposure to BSE through contaminated food caused the appearance of the new variant form of CJD (vCJD). These diseases are caused by an abnormal prion protein named PrPSc (or prion), which accumulates in the brain and leads to the onset of the disease. Their definite diagnosis can be formulated only at post-mortem after biochemical and neuropathological identification of PrPSc. Thanks to the advent of an innovative technique named protein misfolding cyclic amplification (PMCA), traces of PrPSc, undetectable with the standard diagnostic techniques, were found in peripheral tissues of patients with vCJD, even at preclinical stages. The technology is currently being used in specialized laboratories and can be exploited for helping physicians in formulating an early and definite diagnosis of vCJD using peripheral tissues. However, this assay is currently unable to detect prions associated with the sporadic CJD (sCJD) forms, which are more frequent than vCJD. This review will focus on the most recent advances and applications of PMCA in the field of vCJD and other human prion disease diagnosis.<\/jats:p>","DOI":"10.3390\/biom10030405","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T09:26:41Z","timestamp":1583486801000},"page":"405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["PMCA Applications for Prion Detection in Peripheral Tissues of Patients with Variant Creutzfeldt-Jakob Disease"],"prefix":"10.3390","volume":"10","author":[{"given":"Giorgio","family":"Giaccone","sequence":"first","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta, Division of Neurology 5\u2014Neuropathology, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2820-9880","authenticated-orcid":false,"given":"Fabio","family":"Moda","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta, Division of Neurology 5\u2014Neuropathology, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Knight, R., Brazier, M., and Collins, S.J. (2004). Human Prion Diseases: Cause, Clinical and Diagnostic Aspects. Prions, KARGER.","DOI":"10.1159\/000077051"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/bmb\/66.1.213","article-title":"Sporadic and familial CJD: Classification and characterisation","volume":"66","author":"Gambetti","year":"2003","journal-title":"Br. Med. Bull."},{"key":"ref_3","doi-asserted-by":"crossref","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":"ref_4","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1126\/science.1083320","article-title":"Balancing Selection at the Prion Protein Gene Consistent with Prehistoric Kurulike Epidemics","volume":"300","author":"Mead","year":"2003","journal-title":"Science (80-. )"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.neuro.24.1.519","article-title":"Prion Diseases of Humans and Animals: Their Causes and Molecular Basis","volume":"24","author":"Collinge","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s40249-016-0143-8","article-title":"Epidemiological characteristics of human prion diseases","volume":"5","author":"Chen","year":"2016","journal-title":"Infect. Dis. Poverty"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s00439-005-0020-1","article-title":"Genetic prion disease: The EUROCJD experience","volume":"118","author":"Puopolo","year":"2005","journal-title":"Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4138","DOI":"10.1007\/s12035-016-9918-y","article-title":"Hereditary Human Prion Diseases: An Update","volume":"54","author":"Schmitz","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1212\/WNL.42.3.669","article-title":"Fatal familial insomnia: A second kindred with mutation of prion protein gene at codon 178","volume":"42","author":"Medori","year":"1992","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1086\/319997","article-title":"Creutzfeldt-Jakob Disease: Recommendations for Disinfection and Sterilization","volume":"32","author":"Weinstein","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1146\/annurev.mi.43.100189.002021","article-title":"Scrapie Prions","volume":"43","author":"Prusiner","year":"1989","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1097\/ICO.0b013e31816a628d","article-title":"Creutzfeldt-Jakob Disease in Recipients of Corneal Transplants","volume":"27","author":"Maddox","year":"2008","journal-title":"Cornea"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1038\/eye.2008.381","article-title":"Risk of Creutzfeldt\u2013Jakob disease transmission by ocular surgery and tissue transplantation","volume":"23","author":"Armitage","year":"2009","journal-title":"Eye"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1212\/WNL.55.8.1075","article-title":"Iatrogenic Creutzfeldt-Jakob disease at the millennium","volume":"55","author":"Brown","year":"2000","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1159\/000181894","article-title":"Combination Ultrafiltration and 6 MUrea Treatment of Human Growth Hormone Effectively Minimizes Risk from Potential Creutzfeldt-Jakob Disease Virus Contamination","volume":"35","author":"Pocchiari","year":"1991","journal-title":"Horm. Res."},{"key":"ref_16","unstructured":"Moore, R.-A., Vorberg, I., and Priola1, S.-A. (2013). Species barriers in prion diseases\u2014Brief review. Infectious Diseases from Nature: Mechanisms of Viral Emergence and Persistence, Springer-Verlag."},{"key":"ref_17","doi-asserted-by":"crossref","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":"ref_18","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0140-6736(04)16810-4","article-title":"Novel methods for disinfection of prion-contaminated medical devices","volume":"364","author":"Fichet","year":"2004","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bistaffa, E., Rossi, M., De Luca, C.M.G., and Moda, F. (2017). Biosafety of Prions. Progress in Molecular Biology and Translational Science, Academic Press.","DOI":"10.1016\/bs.pmbts.2017.06.017"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.phrp.2012.12.008","article-title":"Prion Diseases as Transmissible Zoonotic Diseases","volume":"4","author":"Lee","year":"2013","journal-title":"Osong Public Health Res. Perspect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/39057","article-title":"Transmissions to mice indicate that \u2018new variant\u2019 CJD is caused by the BSE agent","volume":"389","author":"Bruce","year":"1997","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1093\/brain\/awm063","article-title":"Creutzfeldt-Jakob disease in Germany: A prospective 12-year surveillance","volume":"130","author":"Heinemann","year":"2007","journal-title":"Brain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.neurol.2009.04.006","article-title":"Le r\u00e9seau de surveillance de la maladie de Creutzfeldt-Jakob","volume":"165","author":"Brandel","year":"2009","journal-title":"Rev. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.1093\/brain\/awq216","article-title":"Prospective 10-year surveillance of human prion diseases in Japan","volume":"133","author":"Nozaki","year":"2010","journal-title":"Brain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1159\/000331907","article-title":"Creutzfeldt-Jakob Disease Surveillance in Argentina, 1997\u20132008","volume":"37","author":"Martinetto","year":"2011","journal-title":"Neuroepidemiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/jmv.24004","article-title":"Review: Laboratory diagnosis and surveillance of Creutzfeldt-Jakob disease","volume":"87","author":"Lee","year":"2015","journal-title":"J. Med. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1098\/rsif.2007.0216","article-title":"Is there the potential for an epidemic of variant Creutzfeldt\u2013Jakob disease via blood transfusion in the UK?","volume":"4","author":"Clarke","year":"2007","journal-title":"J. R. Soc. Interface"},{"key":"ref_28","unstructured":"Peden, A.H., Ritchie, D.L., and Ironside, J.W. (2005). Risks of transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Folia Neuropathol., 271\u2013278."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1423-0410.2006.00833.x","article-title":"Creutzfeldt\u2013Jakob disease and blood transfusion: Results of the UK Transfusion Medicine Epidemiological Review study","volume":"91","author":"Hewitt","year":"2006","journal-title":"Vox Sang."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1423-0410.2009.01222.x","article-title":"A retrospective case note review of deceased recipients of vCJD-implicated blood transfusions","volume":"97","author":"Gillies","year":"2009","journal-title":"Vox Sang."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1073\/pnas.95.23.13363","article-title":"Nobel Lecture: Prions","volume":"95","author":"Prusiner","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","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":"ref_33","doi-asserted-by":"crossref","unstructured":"Castle, A.R., and Gill, A.C. (2017). Physiological Functions of the Cellular Prion Protein. Front. Mol. Biosci., 4.","DOI":"10.3389\/fmolb.2017.00019"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.bbapap.2007.05.005","article-title":"Effects of post-translational modifications on prion protein aggregation and the propagation of scrapie-like characteristics in vitro","volume":"1774","author":"Dear","year":"2007","journal-title":"Biochim. Biophys. Acta - Proteins Proteomics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/brain\/awl013","article-title":"Distinct glycoform ratios of protease resistant prion protein associated with PRNP point mutations","volume":"129","author":"Hill","year":"2006","journal-title":"Brain"},{"key":"ref_36","doi-asserted-by":"crossref","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. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1096\/fasebj.5.13.1916104","article-title":"Prions and prion proteins","volume":"5","author":"Stahl","year":"1991","journal-title":"FASEB J."},{"key":"ref_38","doi-asserted-by":"crossref","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":"ref_39","doi-asserted-by":"crossref","first-page":"3654","DOI":"10.1128\/JVI.78.7.3654-3662.2004","article-title":"Comparative Molecular Analysis of the Abnormal Prion Protein in Field Scrapie Cases and Experimental Bovine Spongiform Encephalopathy in Sheep by Use of Western Blotting and Immunohistochemical Methods","volume":"78","author":"Lezmi","year":"2004","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/0962-8924(94)90032-9","article-title":"Molecular biology of prion diseases","volume":"4","author":"Weissmann","year":"1994","journal-title":"Trends Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10168","DOI":"10.1073\/pnas.97.18.10168","article-title":"Genetic influence on the structural variations of the abnormal prion protein","volume":"97","author":"Parchi","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","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":"ref_43","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":"ref_44","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/nrm2204","article-title":"Insights into prion strains and neurotoxicity","volume":"8","author":"Aguzzi","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/bpa.12695","article-title":"Recent advances in the histo-molecular pathology of human prion disease","volume":"29","author":"Baiardi","year":"2019","journal-title":"Brain Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Morales, R. (2017). Prion strains in mammals: Different conformations leading to disease. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006323"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1152\/physrev.00006.2009","article-title":"Prions: Protein Aggregation and Infectious Diseases","volume":"89","author":"Aguzzi","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Miyazono, M., Kitamoto, T., Doh-ura, K., Iwaki, T., and Tateishi, J. (1992). Creutzfeldt-Jakob disease with codon 129 polymorphism (Valine): A comparative study of patients with codon 102 point mutation or without mutations. Acta Neuropathol., 84.","DOI":"10.1007\/BF00227660"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/0304-3940(94)90932-6","article-title":"Neuropathological phenotype and \u2018prion protein\u2019 genotype correlation in sporadic Creutzfeldt-Jakob disease","volume":"179","author":"Ironside","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1093\/bmb\/66.1.241","article-title":"Molecular and clinical classification of human prion disease","volume":"66","author":"Wadsworth","year":"2003","journal-title":"Br. Med. Bull."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/ana.20127","article-title":"Prion protein heterogeneity in sporadic but not variant Creutzfeldt-Jakob disease: U.K. cases 1991-2002","volume":"55","author":"Head","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/383685a0","article-title":"Molecular analysis of prion strain variation and the aetiology of \u201cnew variant\u201d CJD","volume":"383","author":"Collinge","year":"1996","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/nn.3120","article-title":"Prion propagation, toxicity and degradation","volume":"15","author":"Aguzzi","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Mabbott, N. (2017). How do PrPSc Prions Spread between Host Species, and within Hosts?. Pathogens, 6.","DOI":"10.3390\/pathogens6040060"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/35081095","article-title":"Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding","volume":"411","author":"Saborio","year":"2001","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Moda, F. (2017). Protein Misfolding Cyclic Amplification of Infectious Prions. Progress in Molecular Biology and Translational Science, Academic Press.","DOI":"10.1016\/bs.pmbts.2017.06.016"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"35245","DOI":"10.1074\/jbc.M603964200","article-title":"Ultra-efficient Replication of Infectious Prions by Automated Protein Misfolding Cyclic Amplification","volume":"281","author":"Castilla","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12207","DOI":"10.1073\/pnas.0404650101","article-title":"Autocatalytic self-propagation of misfolded prion protein","volume":"101","author":"Bieschke","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1038\/nprot.2012.067","article-title":"Protein misfolding cyclic amplification of infectious prions","volume":"7","author":"Morales","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Gonzalez-Montalban, N., Makarava, N., Ostapchenko, V.G., Savtchenk, R., Alexeeva, I., Rohwer, R.G., and Baskakov, I.V. (2011). Highly Efficient Protein Misfolding Cyclic Amplification. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1001277"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Green, K.M., Castilla, J., Seward, T.S., Napier, D.L., Jewell, J.E., Soto, C., and Telling, G.C. (2008). Accelerated High Fidelity Prion Amplification Within and Across Prion Species Barriers. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000139"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Moudjou, M., Sibille, P., Fichet, G., Reine, F., Chapuis, J., Herzog, L., Jaumain, E., Laferri\u00e8re, F., Richard, C.-A., and Laude, H. (2013). Highly Infectious Prions Generated by a Single Round of Microplate-Based Protein Misfolding Cyclic Amplification. MBio, 5.","DOI":"10.1128\/mBio.00829-13"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cell.2005.02.011","article-title":"In Vitro Generation of Infectious Scrapie Prions","volume":"121","author":"Castilla","year":"2005","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","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":"ref_65","doi-asserted-by":"crossref","unstructured":"B\u00e9londrade, M., Jas-Duval, C., Nicot, S., Bruy\u00e8re-Ostells, L., Mayran, C., Herzog, L., Reine, F., Torres, J.M., Fournier-Wirth, C., and B\u00e9ringue, V. (2020). Correlation between Bioassay and Protein Misfolding Cyclic Amplification for Variant Creutzfeldt-Jakob Disease Decontamination Studies. mSphere, 5.","DOI":"10.1128\/mSphere.00649-19"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1056\/NEJMoa1404401","article-title":"Prions in the Urine of Patients with Variant Creutzfeldt\u2013Jakob Disease","volume":"371","author":"Moda","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_67","first-page":"370ra183","article-title":"Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease","volume":"8","author":"Pritzkow","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_68","doi-asserted-by":"crossref","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":"ref_69","doi-asserted-by":"crossref","unstructured":"(2019). Prion 2019 emerging concepts. Prion, 13, 1\u2013141.","DOI":"10.1080\/19336896.2019.1615197"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1056\/NEJM199609263351303","article-title":"The 14-3-3 Brain Protein in Cerebrospinal Fluid as a Marker for Transmissible Spongiform Encephalopathies","volume":"335","author":"Hsich","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1212\/WNL.58.2.192","article-title":"Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt\u2013Jakob disease","volume":"58","author":"Otto","year":"2002","journal-title":"Neurology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1148\/radiology.199.3.8638007","article-title":"MR imaging of Creutzfeldt-Jakob disease","volume":"199","author":"Finkenstaedt","year":"1996","journal-title":"Radiology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1750-3639.2000.tb00240.x","article-title":"Creutzfeldt-Jakob Disease: Carnoy\u2019s Fixative Improves the Immunohistochemistry of the Proteinase K- Resistant Prion Protein","volume":"10","author":"Giaccone","year":"2006","journal-title":"Brain Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Ladogana, A., and Kovacs, G.G. (2018). Genetic Creutzfeldt\u2013Jakob disease. Handbook of Clinical Neurology, Elsevier.","DOI":"10.1016\/B978-0-444-63945-5.00013-1"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nm.2294","article-title":"Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion","volume":"17","author":"Atarashi","year":"2011","journal-title":"Nat. Med."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Soto, C. (2004). Diagnosing prion diseases: Needs, challenges and hopes. Nat. Rev. Microbiol.","DOI":"10.1038\/nrmicro1003"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3201\/eid2001.130353","article-title":"Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease","volume":"20","author":"Douet","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3201\/eid1801.110589","article-title":"Assessing Prion Infectivity of Human Urine in Sporadic Creutzfeldt-Jakob Disease","volume":"18","author":"Notari","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/BF00690454","article-title":"Experimental transmission of human subacute spongiform encephalopathy to small rodents","volume":"51","author":"Tateishi","year":"1980","journal-title":"Acta Neuropathol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1128\/iai.41.1.154-161.1983","article-title":"Creutzfeldt-Jakob disease in mice: Persistent viremia and preferential replication of virus in low-density lymphocytes","volume":"41","author":"Kuroda","year":"1983","journal-title":"Infect. Immun."},{"key":"ref_81","doi-asserted-by":"crossref","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":"ref_82","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1093\/brain\/awg125","article-title":"Molecular classification of sporadic Creutzfeldt\u2013Jakob disease","volume":"126","author":"Hill","year":"2003","journal-title":"Brain"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"31479","DOI":"10.1074\/jbc.C100278200","article-title":"A Protease-resistant Prion Protein Isoform Is Present in Urine of Animals and Humans Affected with Prion Diseases","volume":"276","author":"Shaked","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"23661","DOI":"10.1074\/jbc.M400187200","article-title":"A Pitfall in Diagnosis of Human Prion Diseases Using Detection of Protease-resistant Prion Protein in Urine","volume":"279","author":"Furukawa","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"48817","DOI":"10.1074\/jbc.M409107200","article-title":"Immunoglobulins in Urine of Hamsters with Scrapie","volume":"279","author":"Serban","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1212\/01.WNL.0000161842.68793.8A","article-title":"Evaluation of urinary PrPSc as a diagnostic test for sporadic, variant, and familial CJD","volume":"64","author":"Head","year":"2005","journal-title":"Neurology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1056\/NEJMoa030351","article-title":"Extraneural Pathologic Prion Protein in Sporadic Creutzfeldt\u2013Jakob Disease","volume":"349","author":"Glatzel","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"927","DOI":"10.2353\/ajpath.2006.050788","article-title":"Detection and Localization of PrPSc in the Skeletal Muscle of Patients with Variant, Iatrogenic, and Sporadic Forms of Creutzfeldt-Jakob Disease","volume":"168","author":"Peden","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7944","DOI":"10.1523\/JNEUROSCI.2467-05.2005","article-title":"Chronic Wasting Disease of Elk: Transmissibility to Humans Examined by Transgenic Mouse Models","volume":"25","author":"Kong","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0140-6736(10)62308-2","article-title":"Detection of prion infection in variant Creutzfeldt-Jakob disease: A blood-based assay","volume":"377","author":"Edgeworth","year":"2011","journal-title":"Lancet"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1001\/jamaneurol.2013.6001","article-title":"Population Screening for Variant Creutzfeldt-Jakob Disease Using a Novel Blood Test","volume":"71","author":"Jackson","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1182\/blood-2013-11-539239","article-title":"A highly specific blood test for vCJD","volume":"123","author":"Jackson","year":"2014","journal-title":"Blood"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Lacroux, C., Comoy, E., Moudjou, M., Perret-Liaudet, A., Lugan, S., Litaise, C., Simmons, H., Jas-Duval, C., Lantier, I., and B\u00e9ringue, V. (2014). Preclinical Detection of Variant CJD and BSE Prions in Blood. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004202"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"370ra182-370ra182","DOI":"10.1126\/scitranslmed.aag1257","article-title":"Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease","volume":"8","author":"Bougard","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3201\/eid2601.181423","article-title":"Preclinical Detection of Prions in Blood of Nonhuman Primates Infected with Variant Creutzfeldt-Jakob Disease","volume":"26","author":"Chacon","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Urwin, P., Thanigaikumar, K., Ironside, J.W., Molesworth, A., Knight, R.S., Hewitt, P.E., Llewelyn, C., Mackenzie, J., and Will, R.G. (2017). Sporadic Creutzfeldt-Jakob Disease in 2 Plasma Product Recipients, United Kingdom. Emerg. Infect. Dis., 23.","DOI":"10.3201\/eid2306.161884"},{"key":"ref_97","doi-asserted-by":"crossref","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":"ref_98","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1056\/NEJMc1610003","article-title":"Variant Creutzfeldt\u2013Jakob Disease in a Patient with Heterozygosity at PRNP Codon 129","volume":"376","author":"Mok","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1016\/S0140-6736(06)68930-7","article-title":"Kuru in the 21st century\u2014An acquired human prion disease with very long incubation periods","volume":"367","author":"Collinge","year":"2006","journal-title":"Lancet"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.3201\/eid2407.172105","article-title":"Diagnosis of Methionine\/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification","volume":"24","author":"Bougard","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1056\/NEJMoa1315200","article-title":"A Test for Creutzfeldt\u2013Jakob Disease Using Nasal Brushings","volume":"371","author":"Bongianni","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"f5675","DOI":"10.1136\/bmj.f5675","article-title":"Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: Large scale survey","volume":"347","author":"Gill","year":"2013","journal-title":"BMJ"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Diack, A.B., Will, R.G., and Manson, J.C. (2017). Public health risks from subclinical variant CJD. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006642"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Johnson, C.J., Aiken, J.M., McKenzie, D., Samuel, M.D., and Pedersen, J.A. (2012). Highly Efficient Amplification of Chronic Wasting Disease Agent by Protein Misfolding Cyclic Amplification with Beads (PMCAb). PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035383"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.3201\/eid2408.161888","article-title":"Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions","volume":"24","author":"Barria","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Houston, F., and Andr\u00e9oletti, O. (2018). The zoonotic potential of animal prion diseases. Handbook of Clinical Neurology, Elsevier.","DOI":"10.1016\/B978-0-444-63945-5.00025-8"},{"key":"ref_107","doi-asserted-by":"crossref","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":"ref_108","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/ana.23589","article-title":"Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease","volume":"72","author":"McGuire","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/ana.24679","article-title":"Cerebrospinal fluid real-time quaking-induced conversion is a robust and reliable test for sporadic creutzfeldt-jakob disease: An international study","volume":"80","author":"McGuire","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.celrep.2014.02.031","article-title":"Detection of Misfolded A\u03b2 Oligomers for Sensitive Biochemical Diagnosis of Alzheimer\u2019s Disease","volume":"7","author":"Salvadores","year":"2014","journal-title":"Cell Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1001\/jamaneurol.2016.4547","article-title":"Development of a Biochemical Diagnosis of Parkinson Disease by Detection of \u03b1-Synuclein Misfolded Aggregates in Cerebrospinal Fluid","volume":"74","author":"Shahnawaz","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1002\/mds.27646","article-title":"Comparative study of cerebrospinal fluid \u03b1-synuclein seeding aggregation assays for diagnosis of Parkinson\u2019s disease","volume":"34","author":"Kang","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40478-018-0508-2","article-title":"Rapid and ultra-sensitive quantitation of disease-associated \u03b1-synuclein seeds in brain and cerebrospinal fluid by \u03b1Syn RT-QuIC","volume":"6","author":"Groveman","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/acn3.338","article-title":"Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies","volume":"3","author":"Fairfoul","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"23029","DOI":"10.1073\/pnas.1909322116","article-title":"Million-fold sensitivity enhancement in proteopathic seed amplification assays for biospecimens by Hofmeister ion comparisons","volume":"116","author":"Metrick","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s00401-017-1692-z","article-title":"Ultrasensitive and selective detection of 3-repeat tau seeding activity in Pick disease brain and cerebrospinal fluid","volume":"133","author":"Saijo","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00401-019-02080-2","article-title":"4-Repeat tau seeds and templating subtypes as brain and CSF biomarkers of frontotemporal lobar degeneration","volume":"139","author":"Saijo","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_118","doi-asserted-by":"crossref","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":"Elia","year":"2019","journal-title":"Transl. Neurodegener."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/s41586-020-1984-7","article-title":"Discriminating \u03b1-synuclein strains in Parkinson\u2019s disease and multiple system atrophy","volume":"578","author":"Shahnawaz","year":"2020","journal-title":"Nature"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/3\/405\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:04:38Z","timestamp":1760173478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/3\/405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,5]]},"references-count":119,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["biom10030405"],"URL":"https:\/\/doi.org\/10.3390\/biom10030405","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,5]]}}}