title: Subtype and regional regulation of prion biomarkers in sporadic Creutzfeldt-Jakob disease.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical School, Georg-August University and German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.|Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Franc
authors.initials: F
authors.lastname: Llorens
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical School, Georg-August University and German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Saima
authors.initials: S
authors.lastname: Zafar
authors.affiliation: Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.|CIBERNED (Network Center for Biomedical Research of Neurodegenerative Diseases), Institute Carlos III, Ministry of Health, Barcelona, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Ansoleaga
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical School, Georg-August University and German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Mohsin
authors.initials: M
authors.lastname: Shafiq
authors.affiliation: Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.|CIBERNED (Network Center for Biomedical Research of Neurodegenerative Diseases), Institute Carlos III, Ministry of Health, Barcelona, Spain.
authors.forename: Rosi
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.|CIBERNED (Network Center for Biomedical Research of Neurodegenerative Diseases), Institute Carlos III, Ministry of Health, Barcelona, Spain.
authors.forename: Marga
authors.initials: M
authors.lastname: Carmona
authors.affiliation: CJD-Unit and Alzheimer disease and other cognitive disorders Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Grau-Rivera
authors.affiliation: General Subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Nos
authors.affiliation: Neurological Tissue Bank of the Biobanc-Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Ellen
authors.initials: E
authors.lastname: Gelpí
authors.affiliation: CIBERNED (Network Center for Biomedical Research of Neurodegenerative Diseases), Institute Carlos III, Ministry of Health, Barcelona, Spain.|Molecular and Cellular Neurobiotechnology, Catalonian Institute for Bioengineering (IBEC), Parc Científic de Barcelona, Barcelona, Spain.|Department of Cell Biology, University of Barcelona, Barcelona, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Del Río
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical School, Georg-August University and German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
authors.affiliation: Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.|CIBERNED (Network Center for Biomedical Research of Neurodegenerative Diseases), Institute Carlos III, Ministry of Health, Barcelona, Spain.
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011328:Prions / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid / Q000378:metabolism; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D015415:Biomarkers; C054369:MAPT protein, human; D011328:Prions; D051844:alpha-Synuclein; D016875:tau Proteins
keywords: Creutzfeldt-Jakob disease; cerebrospinal fluid; disease subtype; glycogen synthase kinase 3; prion biomarkers; prion protein