{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:19:48Z","timestamp":1776932388972,"version":"3.51.2"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009553","name":"Agentura Pro Zdravotnick\u00fd V\u00fdzkum \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["NU23\u201004\u201000173"],"award-info":[{"award-number":["NU23\u201004\u201000173"]}],"id":[{"id":"10.13039\/501100009553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Formalin\u2010fixed paraffin\u2010embedded (FFPE) samples, routinely used in neuropathology, represent an invaluable resource for studying rare diseases like transmissible spongiform encephalopathies (TSE). Despite fixation\u2010induced protein cross\u2010linking, prion seeding activity can be effectively detected using the seeding amplification assays. In this study, we employed the second\u2010generation real\u2010time quaking\u2010induced conversion (RT\u2010QuIC) assay to analyse and quantify human prion seeding activity in FFPE brain tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>FFPE frontal brain tissues were deparaffinised in xylene, followed by rehydration through descending concentrations of ethanol. The prion seeding activity in tissue homogenates was assessed by RT\u2010QuIC assay utilising short recombinant hamster prion protein (rHaPrP90\u2010231) as a substrate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 60 samples, including 30 cases of confirmed TSE, comprising both sporadic and genetic forms, as well as 30 non\u2010TSE controls, were analysed. Prion seeding activity has been detected in all TSE samples except one sCJD (VV2) and one GSS (P102L) case, corresponding to an assay sensitivity of 93.3%. Conversely, we did not detect any RT\u2010QuIC positivity in the control group, resulting in 100% specificity. The mean 50% prion seeding dose of FFPE sporadic TSE samples was 10<jats:sup>7.8<\/jats:sup>\/g of brain tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study emphasises high sensitivity and specificity of RT\u2010QuIC assay for prion detection in archival human FFPE brain tissues and demonstrates its diagnostic reliability comparable to other tissue types even after years of storage. The applicability of FFPE samples in RT\u2010QuIC assays facilitates retrospective diagnostics and provides logistical advantages for sample preservation and transportation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.70028","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T13:20:26Z","timestamp":1752067226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Detection of Human Prion Seeding Activity in Formalin\u2010Fixed Paraffin\u2010Embedded Archival Tissues"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0188-0241","authenticated-orcid":false,"given":"So\u0148a","family":"Baranov\u00e1","sequence":"first","affiliation":[{"name":"Prion Research Laboratory, Institute of Medical Microbiology, First Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6152-6343","authenticated-orcid":false,"given":"Radoslav","family":"Mat\u011bj","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Third Faculty of Medicine Charles University and Thomayer University Hospital  Prague Czech Republic"},{"name":"Department of Pathology, First Faculty of Medicine Charles University, and General University Hospital  Prague Czech Republic"},{"name":"Brain Bank, Third Faculty of Medicine Charles University and Thomayer University Hospital  Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiri\u00a0G.","family":"Safar","sequence":"additional","affiliation":[{"name":"Department of Pathology Case Western Reserve University School of Medicine  Cleveland Ohio USA"},{"name":"Department of Neurology Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karel","family":"Holada","sequence":"additional","affiliation":[{"name":"Prion Research Laboratory, Institute of Medical Microbiology, First Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51219"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360330915"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560021220"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep25098"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27907"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28242"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2022.08.012"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-56789-6"},{"key":"e_1_2_12_10_1","unstructured":"World Health Organization \u201cWHO Manual for Surveillance of Human Transmissible Spongiform Encephalopathies Including Variant Creutzfeldt\u2010Jakob Disease \u201d World Health Organization; (2003) 90p https:\/\/iris.who.int\/handle\/10665\/42656."},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24833"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10060750"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02451\u201014"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001217"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2021.105504"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1087982"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02162\u201016"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.4797"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-024-06886-6"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84527-9"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.874734"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054915"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70028","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T04:40:39Z","timestamp":1760503239000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.70028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,9]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/nan.70028"],"URL":"https:\/\/doi.org\/10.1111\/nan.70028","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,9]]},"assertion":[{"value":"2025-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70028"}}