{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:58:23Z","timestamp":1785938303559,"version":"3.56.0"},"reference-count":6,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Genetic Creutzfeldt\u2013Jakob disease (gCJD) is a rare inherited prion disorder caused by pathogenic variants in the\n                      <jats:italic>PRNP<\/jats:italic>\n                      gene. Slovakia represents one of the major endemic regions worldwide, with most genetic cases linked to the E200K variant. Reliable cerebrospinal fluid (CSF) biomarkers remain important for diagnosis and surveillance in this setting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed CSF samples from 77 consecutive symptomatic patients with genetically confirmed E200K gCJD referred to the National Reference Centre for Prion Diseases in Slovakia between 2020 and 2024. Total tau (T-tau) concentrations were measured by ELISA and 14-3-3 protein was detected by Western blot as part of the routine diagnostic evaluation throughout the study period. Real-time quaking-induced conversion (RT-QuIC) was introduced in 2023 and was performed prospectively thereafter, while archived frozen CSF samples collected earlier were analyzed retrospectively. Diagnostic sensitivity was evaluated overall and according to the\n                      <jats:italic>PRNP<\/jats:italic>\n                      codon 129 genotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RT-QuIC showed the highest sensitivity (75\/77; 97.4%), followed by T-tau (64\/77; 83.1%) and 14-3-3 protein (42\/77; 54.5%). RT-QuIC was positive in all methionine\/valine heterozygotes (30\/30; 100%) and in 45 of 47 methionine homozygotes (95.7%) (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.518). In contrast, T-tau and 14-3-3 protein demonstrated significantly higher sensitivity in methionine homozygotes than in heterozygotes (both\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      RT-QuIC showed the highest diagnostic sensitivity among the evaluated CSF biomarkers in this endemic cohort. Conventional biomarkers showed marked dependence on\n                      <jats:italic>PRNP<\/jats:italic>\n                      codon 129 genotype and may provide complementary diagnostic value.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1906444","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:41:54Z","timestamp":1785937314000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerebrospinal fluid biomarkers in E200K genetic Creutzfeldt\u2013Jakob disease: a national study from an endemic Slovak cohort"],"prefix":"10.3389","volume":"20","author":[{"given":"Dana","family":"Zakova","sequence":"first","affiliation":[{"name":"National Reference Centre for Prion Diseases, Slovak Medical University","place":["Bratislava, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Koscova","sequence":"additional","affiliation":[{"name":"National Reference Centre for Prion Diseases, Slovak Medical University","place":["Bratislava, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Melicherova","sequence":"additional","affiliation":[{"name":"National Reference Centre for Prion Diseases, Slovak Medical University","place":["Bratislava, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alzbeta","family":"Janakova","sequence":"additional","affiliation":[{"name":"National Reference Centre for Prion Diseases, Slovak Medical University","place":["Bratislava, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Szarvasova","sequence":"additional","affiliation":[{"name":"National Reference Centre for Prion Diseases, Slovak Medical University","place":["Bratislava, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Kosorinova","sequence":"additional","affiliation":[{"name":"National Reference Centre for Prion Diseases, Slovak Medical University","place":["Bratislava, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Stelzer","sequence":"additional","affiliation":[{"name":"National Reference Centre for Prion Diseases, Slovak Medical University","place":["Bratislava, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"150","DOI":"10.4161\/pri.5.3.16893","article-title":"Real-time quaking-induced conversion","volume":"5","author":"Atarashi","year":"2011","journal-title":"Prion"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"5919","DOI":"10.1007\/s12035-016-0128-4","article-title":"Cerebrospinal fluid biomarkers in the diagnosis of Creutzfeldt-Jakob disease in Slovak patients: over 10-year period review","volume":"54","author":"Koscova","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/BF00143126","article-title":"Focal accumulation of CJD in Slovakia: retrospective investigation of a new rural familial cluster","volume":"7","author":"Mitrova","year":"1991","journal-title":"Eur. J. Epidemiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1212\/01.wnl.0000230159.67128.00","article-title":"CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease","volume":"67","author":"Sanchez-Juan","year":"2006","journal-title":"Neurology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1093\/brain\/awab350","article-title":"Diagnostic accuracy of cerebrospinal fluid biomarkers in genetic prion diseases","volume":"145","author":"Schmitz","year":"2022","journal-title":"Brain"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.1093\/brain\/awp191","article-title":"Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease","volume":"132","author":"Zerr","year":"2009","journal-title":"Brain"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1906444\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:41:55Z","timestamp":1785937315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1906444\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":6,"alternative-id":["10.3389\/fnins.2026.1906444"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2026.1906444","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"article-number":"1906444"}}