{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:40:58Z","timestamp":1792885258002,"version":"4.5.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,1,20]],"date-time":"2015-01-20T00:00:00Z","timestamp":1421712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2015,2,27]],"date-time":"2015-02-27T00:00:00Z","timestamp":1424995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2015,2,27]]},"abstract":"<jats:title>ABSTRACT\u2002<\/jats:title>\n          <jats:p>\n            Fast, definitive diagnosis of Creutzfeldt-Jakob disease (CJD) is important in assessing patient care options and transmission risks. Real-time quaking-induced conversion (RT-QuIC) assays of cerebrospinal fluid (CSF) and nasal-brushing specimens are valuable in distinguishing CJD from non-CJD conditions but have required 2.5 to 5\u00a0days. Here, an improved RT-QuIC assay is described which identified positive CSF samples within 4 to 14 h with better analytical sensitivity. Moreover, analysis of 11 CJD patients demonstrated that while 7 were RT-QuIC positive using the previous conditions, 10 were positive using the new assay. In these and further analyses, a total of 46 of 48 CSF samples from sporadic CJD patients were positive, while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity and 100% specificity. This second-generation RT-QuIC assay markedly improved the speed and sensitivity of detecting prion seeds in CSF specimens from CJD patients. This should enhance prospects for rapid and accurate\n            <jats:italic>ante mortem<\/jats:italic>\n            CJD diagnosis.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            A long-standing problem in dealing with various neurodegenerative protein misfolding diseases is early and accurate diagnosis. This issue is particularly important with human prion diseases, such as CJD, because prions are deadly, transmissible, and unusually resistant to decontamination. The recently developed RT-QuIC test allows for highly sensitive and specific detection of CJD in human cerebrospinal fluid and is being broadly implemented as a key diagnostic tool. However, as currently applied, RT-QuIC takes 2.5 to 5\u00a0days and misses 11 to 23% of CJD cases. Now, we have markedly improved RT-QuIC analysis of human CSF such that CJD and non-CJD patients can be discriminated in a matter of hours rather than days with enhanced sensitivity. These improvements should allow for much faster, more accurate, and practical testing for CJD. In broader terms, our study provides a prototype for tests for misfolded protein aggregates that cause many important amyloid diseases, such as Alzheimer\u2019s, Parkinson\u2019s, and tauopathies.\n          <\/jats:p>","DOI":"10.1128\/mbio.02451-14","type":"journal-article","created":{"date-parts":[[2015,1,21]],"date-time":"2015-01-21T04:58:11Z","timestamp":1421816291000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":213,"title":["Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease Using Cerebrospinal Fluid"],"prefix":"10.1128","volume":"6","author":[{"given":"Christina D.","family":"Orr\u00fa","sequence":"first","affiliation":[{"name":"Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley R.","family":"Groveman","sequence":"additional","affiliation":[{"name":"Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Hughson","sequence":"additional","affiliation":[{"name":"Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Zanusso","sequence":"additional","affiliation":[{"name":"Department of Neurological and Movement Sciences, University of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Coulthart","sequence":"additional","affiliation":[{"name":"Canadian CJD Surveillance System, Public Health Agency of Canada, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Caughey","sequence":"additional","affiliation":[{"name":"Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1806.120116"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.23.10962"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/382180a0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/306476a0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(83)90168-X"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-5521(95)90087-X"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03989"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(83)90207-6"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00245a003"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","unstructured":"Safar J Roller PP Gajdusek DC Gibbs CJ Jr. 1993. Conformational transitions dissociation and unfolding of scrapie amyloid (prion) protein. 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Animal virus titration techniques, p 183\u2013186. In Harris RJC (ed), Techniques in experimental virology. 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