{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:00:10Z","timestamp":1761541210404},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T00:00:00Z","timestamp":1430352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Seventh Framework Program of the European Commission DEVELAGE project"},{"name":"PRIORITY project"},{"name":"European Union Joint Program DEMTEST"},{"name":"Spanish Ministry of Health, Instituto Carlos III","award":["FIS PI1100968"],"award-info":[{"award-number":["FIS PI1100968"]}]},{"name":"CIBERNED project BESAD-P"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2015,8]]},"abstract":"Aims<\/jats:title>C<\/jats:styled-content>reutzfeldt\u2013J<\/jats:styled-content>akob disease (CJD<\/jats:styled-content>) is a rapid progressive neurological disease leading to dementia and death. Prion biomarkers are altered in the cerebrospinal fluid (CSF<\/jats:styled-content>) of CJD<\/jats:styled-content> patients, but the pathogenic mechanisms underlying these alterations are still unknown. The present study examined prion biomarker levels in the brain and CSF<\/jats:styled-content> of sporadic CJD<\/jats:styled-content> (sCJD<\/jats:styled-content>) cases and their correlation with neuropathological lesion profiles.<\/jats:p><\/jats:sec>Methods<\/jats:title>The expression levels of 14\u20103\u20103, T<\/jats:styled-content>au, phospho\u2010T<\/jats:styled-content>au and \u03b1\u2010synuclein were measured in the CSF<\/jats:styled-content> and brain of sCJD<\/jats:styled-content> cases in a subtype\u2010 and region\u2010specific manner. In addition, the activity of prion biomarker kinases, the expression levels of CJD<\/jats:styled-content> hallmarks and the most frequent neuropathological sCJD<\/jats:styled-content> findings were analysed.<\/jats:p><\/jats:sec>Results<\/jats:title>Prion biomarkers levels were increased in the CSF<\/jats:styled-content> of sCJD<\/jats:styled-content> patients; however, correlations between mRNA<\/jats:styled-content>, total protein and their phosphorylated forms in brain were different. The observed downregulation of the main T<\/jats:styled-content>au kinase, GSK3<\/jats:styled-content>, in sCJD<\/jats:styled-content> brain samples may help to explain the differential phospho\u2010T<\/jats:styled-content>au\/T<\/jats:styled-content>au ratios between sCJD<\/jats:styled-content> and other dementias in the CSF<\/jats:styled-content>. Importantly, CSF<\/jats:styled-content> biomarkers levels do not necessarily correlate with sCJD<\/jats:styled-content> neuropathological findings.<\/jats:p><\/jats:sec>Interpretation<\/jats:title>Present findings indicate that prion biomarkers levels in sCJD<\/jats:styled-content> tissues and their release into the CSF<\/jats:styled-content> are differentially regulated following specific modulated responses, and suggest a functional role for these proteins in sCJD<\/jats:styled-content> pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12175","type":"journal-article","created":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T04:03:25Z","timestamp":1408421005000},"page":"631-645","source":"Crossref","is-referenced-by-count":21,"title":["Subtype and regional regulation of prion biomarkers in sporadic C<\/scp>reutzfeldt\u2013J<\/scp>akob disease"],"prefix":"10.1111","volume":"41","author":[{"given":"Franc","family":"Llorens","sequence":"first","affiliation":[{"name":"Department of Neurology Clinical Dementia Center University Medical School Georg\u2010August University and German Center for Neurodegenerative Diseases (DZNE) G\u00f6ttingen Germany"},{"name":"Institute of Neuropathology IDIBELL\u2010University Hospital Bellvitge University of Barcelona, Hospitalet de Llobregat Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saima","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Neurology Clinical Dementia Center University Medical School Georg\u2010August University and German Center for Neurodegenerative Diseases (DZNE) G\u00f6ttingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bel\u00e9n","family":"Ansoleaga","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology IDIBELL\u2010University Hospital Bellvitge 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