Subtype and regional regulation of prion biomarkers in sporadic Creutzfeldt–Jakob disease. (30th April 2015)

• Record Type: Journal Article
• Authors: Llorens, Franc; Zafar, Saima; Ansoleaga, Belén; Shafiq, Mohsin; Blanco, Rosi; Carmona, Marga; Grau‐Rivera, Oriol; Nos, Carlos; Gelpí, Ellen; del Río, José Antonio; Zerr, Inga; Ferrer, Isidre
• Is Part Of: Neuropathology & applied neurobiology. Volume 41:Number 5(2015)
• Page Start: 631
• Page End: 645
• Publication Date: 2015-04-30
• Subjects: Nervous system -- Diseases -- Pathology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/nan.12175
• Languages: English
• ISSNs: 0305-1846

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="nan12175-sec-0001" sec-type="section"> <title>Aims</title> <p>Creutzfeldt–Jakob disease (CJD) is a rapid progressive neurological disease leading to dementia and death. Prion biomarkers are altered in the cerebrospinal fluid (CSF) of CJD patients, but the pathogenic mechanisms underlying these alterations are still unknown. The present study examined prion biomarker levels in the brain and CSF of sporadic CJD (sCJD) cases and their correlation with neuropathological lesion profiles.</p> </sec> <sec id="nan12175-sec-0002" sec-type="section"> <title>Methods</title> <p>The expression levels of 14‐3‐3, Tau, phospho‐Tau and α‐synuclein were measured in the CSF and brain of sCJD cases in a subtype‐ and region‐specific manner. In addition, the activity of prion biomarker kinases, the expression levels of CJD hallmarks and the most frequent neuropathological sCJD findings were analysed.</p> </sec> <sec id="nan12175-sec-0003" sec-type="section"> <title>Results</title> <p>Prion biomarkers levels were increased in the CSF of sCJD patients; however, correlations between mRNA, total protein and their phosphorylated forms in brain were different. The observed downregulation of the main Tau kinase, GSK3, in sCJD brain samples may help to explain the differential phospho‐Tau/Tau ratios between sCJD and other dementias in the CSF. Importantly, CSF biomarkers levels do not necessarily correlate with sCJD neuropathological findings.</p> </sec> <sec id="nan12175-sec-0004" sec-type="section"> <title>Interpretation</title> <p>Present findings indicate that prion biomarkers levels in sCJD tissues and their release into the CSF are differentially regulated following specific modulated responses, and suggest a functional role for these proteins in sCJD pathogenesis.</p> </sec> </abstract>