Premium
Subtype and regional regulation of prion biomarkers in sporadic C reutzfeldt– J akob disease
Author(s) -
Llorens Franc,
Zafar Saima,
Ansoleaga Belén,
Shafiq Mohsin,
Blanco Rosi,
Carmona Marga,
GrauRivera Oriol,
Nos Carlos,
Gelpí Ellen,
Río José Antonio,
Zerr Inga,
Ferrer Isidre
Publication year - 2015
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12175
Subject(s) - cerebrospinal fluid , pathogenesis , biomarker , creutzfeldt jakob syndrome , downregulation and upregulation , dementia , pathology , tau protein , disease , biology , alzheimer's disease , medicine , immunology , prion protein , gene , genetics
Aims C reutzfeldt– J akob 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. Methods The expression levels of 14‐3‐3, T au, phospho‐ T au 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. Results 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 T au kinase, GSK3 , in sCJD brain samples may help to explain the differential phospho‐ T au/ T au ratios between sCJD and other dementias in the CSF . Importantly, CSF biomarkers levels do not necessarily correlate with sCJD neuropathological findings. Interpretation 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.