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.

Department of Pathology and Molecular Medicine National Reference Laboratory for Diagnostics of Human Prion Diseases Thomayer Hospital Prague Czech Republic Institute of Pathology 3rd Medical Faculty of Charles University Prague and Kralovske Vinohrady Teaching Hospital Prague Czech Republic

Department of Pathology and Molecular Medicine National Reference Laboratory for Diagnostics of Human Prion Diseases Thomayer Hospital Prague Czech Republic Institute of Pathology 3rd Medical Faculty of Charles University Prague and Kralovske Vinohrady Teaching Hospital Prague Czech Republic Department of Neurology and Centre of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Prague Czech Republic

Department of Software Engineering Faculty of Nuclear Science and Physical Engineering Czech Technical University Prague Czech Republic

Thomayer Hospital Department of Neurology Prague Czech Republic Department of Neurology and Centre of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Prague Czech Republic

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