Creutzfeldt-Jakob Disease: Cerebrospinal Fluid Total and Phosphorylated Tau

MedicalResearch.com Interview with:
Tobias Skillbäck, MD
Clinical Neurochemistry Laboratory
Institute of Neuroscience and Physiology
Department of Neurochemistry, Sahlgrenska Academy
University of Gothenburg Mölndal, Sweden

MedicalResearch.com: What are the main findings of the study?

Dr. Skillbäck: There were two main findings in this study.

First; Levels of t-tau and the T-tau/P-tau ratio in CSF of CJD (Creutzfeldt-Jakob Disease) patients are markedly increased, as compared to patients with Alzheimer’s disease and other dementias, and they  are high enough to distinguish CJD against these important differential diagnoses.

Secondly, levels of these biomarkers tend to increase rapidly with disease progress in Creutzfeldt-Jakob Disease. This trend could not be observed for Alzheimer’s disease and other dementias, and could also be used to clinically distinguish CJD and indicates that repeated CSF measurements might be of value if a clinical suspicion of Creutzfeldt-Jakob Diseaseis present.
MedicalResearch.com: Were any of the findings unexpected?

Dr. Skillbäck: That the trend of increasing of tau-levels with disease progression was so clear was not entirely expected. Previous studies have shown more of an upside down U-shaped curve, with increasing tau-levels at the beginning of the disease that reach a peak to subsequently drop before the patients’ demise. This was something we could not find evidence for in this study. The high level of distinction against Alzheimer’s disease (sensitivity, specificity and LR+ was 78.5%, 99.6% and 196.6) and other dementias (78.5%, 99.3% and 109.3) obtained with the threshold values chosen was also a pleasant surprise.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Skillbäck: Assessment of T-tau and the T-tau/P-tau ratio in CSF provides important information in investigations of rapid progressive dementia, and repeated measurements might be of value since Creutzfeldt-Jakob Disease patients show increasing values with disease progress.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Skillbäck:  The next step is to establish the positive and negative predictive values of the tau markers in patients with clinical symptoms making the physician consider Creutzfeldt-Jakob Disease, i.e., in the most relevant clinical context one could imagine. The results of our study suggest that the predictive values will be high and clinically relevant but the precise figures need to be determined. Another important step will be to standardize the T-tau and P-tau markers better. We need certified reference methods and materials for assay calibration making it possible to establish global reference limits and cut-points for the markers.

Citation:

Diagnostic Performance of Cerebrospinal Fluid Total Tau and Phosphorylated Tau in Creutzfeldt-Jakob Disease: Results From the Swedish Mortality Registry

Skillbäck T, Rosén C, Asztely F, Mattsson N, Blennow K, Zetterberg H. Diagnostic Performance of Cerebrospinal Fluid Total Tau and Phosphorylated Tau in Creutzfeldt-Jakob Disease: Results From the Swedish Mortality Registry. JAMA Neurol. 2014;():. doi:10.1001/jamaneurol.2013.6455.

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