title: Proteinase-activated receptor 2 and disease biomarkers in cerebrospinal fluid in cases with autopsy-confirmed prion diseases and other neurodegenerative diseases.
abstract: BACKGROUND
  Proteinase-activated receptor 2 (PAR-2) has been shown to promote both neurotoxic and neuroprotective effects. Similarly, other routinely used nonspecific markers of neuronal damage can be found in cerebrospinal fluid (CSF) and can be used as biomarkers for different neurodegenerative disorders.
  
  
  METHODS
  Using enzyme-linked immunosorbent assays and western blotting we assessed PAR-2, total-tau, phospho-tau, beta-amyloid levels, and protein 14-3-3 in the CSF of former patients who had undergone a neuropathological autopsy after death and who had been definitively diagnosed with a prion or other neurodegenerative disease.
  
  
  RESULTS
  We did not find any significant correlation between levels of PAR-2 and other biomarkers, nor did we find any differences in PAR-2 levels between prion diseases and other neurodegenerative conditions. However, we confirmed that very high total-tau levels were significantly associated with definitive prion diagnoses and exhibited greater sensitivity and specificity than protein 14-3-3, which is routinely used as a marker.
  
  
  CONCLUSIONS
  Our study showed that PAR-2, in CSF, was not specifically altered in prion diseases compared to other neurodegenerative conditions. Our results also confirmed that very high total-tau protein CSF levels were significantly associated with a definitive Creutzfeldt-Jakob disease (CJD) diagnosis and should be routinely tested as a diagnostic marker. Observed individual variability in CSF biomarkers provide invaluable feedback from neuropathological examinations even in "clinically certain" cases.
authors.affiliation: Department of Pathology and Molecular Medicine, National Reference Laboratory for Diagnostics of Human Prion Diseases, Thomayer Hospital, Prague, Czech Republic. zdenek.rohan@ftn.cz.|Institute of Pathology, Third Medical Faculty of Charles University in Prague and Kralovske Vinohrady Teaching Hospital, Prague, Czech Republic. zdenek.rohan@ftn.cz.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Rohan
authors.affiliation: Department of Pathology and Molecular Medicine, National Reference Laboratory for Diagnostics of Human Prion Diseases, Thomayer Hospital, Prague, Czech Republic. magdalena.smetakova@ftn.cz.|Institute of Pathology, Third Medical Faculty of Charles University in Prague and Kralovske Vinohrady Teaching Hospital, Prague, Czech Republic. magdalena.smetakova@ftn.cz.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Smetakova
authors.affiliation: Department of Software Engineering, Faculty of Nuclear Science and Physical Engineering, Czech Technical University, Prague, Czech Republic. jaromir.kukal@fjfi.cvut.cz.
authors.forename: Jaromir
authors.initials: J
authors.lastname: Kukal
authors.affiliation: Thomayer Hospital, Department of Neurology, Prague, Czech Republic. robert.rusina@lf1.cuni.cz.|Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague, and General University Hospital in Prague, Prague, Czech Republic. robert.rusina@lf1.cuni.cz.
authors.forename: Robert
authors.initials: R
authors.lastname: Rusina
authors.affiliation: Department of Pathology and Molecular Medicine, National Reference Laboratory for Diagnostics of Human Prion Diseases, Thomayer Hospital, Prague, Czech Republic. radoslav.matej@ftn.cz.|Institute of Pathology, Third Medical Faculty of Charles University in Prague and Kralovske Vinohrady Teaching Hospital, Prague, Czech Republic. radoslav.matej@ftn.cz.|Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague, and General University Hospital in Prague, Prague, Czech Republic. radoslav.matej@ftn.cz.
authors.forename: Radoslav
authors.initials: R
authors.lastname: Matej
mesh_terms: D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001344:Autopsy; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015153:Blotting, Western; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D015140:Dementia, Vascular / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000134:cerebrospinal fluid / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D010750:Phosphoproteins / Q000134:cerebrospinal fluid; D044464:Receptor, PAR-2 / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013494:Supranuclear Palsy, Progressive / Q000134:cerebrospinal fluid / Q000175:diagnosis; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D048948:14-3-3 Proteins; D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010750:Phosphoproteins; D044464:Receptor, PAR-2; D016875:tau Proteins