The role of proportion of cerebrospinal fluid total Tau-protein and phosphorylated Tau-protein levels in differential diagnosis of CJD

Abstract

Background and Aims:Diagnosis of Creutzfeld-Jacob disease (CJD) is based on typical clinical features and can be supported by detection of 14-3-3 protein in the cerebrospinal fluid (CSF).Present study suggests the importance of investigating the ratio between CSF total tau-protein and CSF phosphorylated tau-protein in differentiating CJD from other dementias.Methods:Thirty-one patients with Alzheimer disease (AD) of Frontotemporal dementia (FTD) and four patients with definitive diagnosis of Creutzfeldt-Jacob disease were included into the study. All study subjects underwent MRI scan of the brain and extended neuropsychiatric examination at baseline to classify the patients as having AD or FTD. Results were compared with an age-matched cognitively normal control group. Tau-protein was analyzed using a commercially available ELISA and 14-3-3 protein was assessed by Western blotting. Three markers were put into comparison: total tau-protein (cutoff value of 355 pg/ml), phosphorylated tau-protein (cutoff value of 55 pg/ml), and beta amyloid (cutoff value of 458 pg/ml). The receiver operating characteristic (ROC) curve has been designed to achieve the best possible sensitivity and specificity for each marker.Results:High ratio between CSF total tau-protein and CSF phosphorylated tau-protein has been found in all patients diagnosed by CJD, even in those with negative 14-3-3 protein blots results. Contrary, marker s analysis in patients with AD revealed the highest ratio between CSF beta amyloid and CSF phosphorylated tau-protein levels.Conclusions:CSF tau-protein and phosphorylated tau-protein are valuable diagnostic biomarkers for CJD, especially in patients with negative 14-3-3 protein findings.