A comparison of tau and 14-3-3 protein in the diagnosis of Creutzfeldt-Jakob disease

Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Neurology (Impact Factor: 8.29). 07/2012; 79(6):547-52. DOI: 10.1212/WNL.0b013e318263565f
Source: PubMed


To compare the respective efficiency of CSF tau (quantitative) and CSF 14-3-3 protein (qualitative) in the diagnosis of prion disease.
We made measurements on 420 live subjects, who subsequently underwent a postmortem neuropathology examination, including protein chemistry, immunohistochemistry, and histology. We performed tau by ELISA. We detected 14-3-3 protein by Western blot. Both assays were optimized for maximum efficiency (accuracy).
We found tau and 14-3-3 proteins to be closely correlated, but tau had a significantly better ability to predict disease status than 14-3-3 protein. Also, tau distinguished disease status at least as well as when both assays' results are combined in a variety of ways. Importantly, the area under the receiver operating characteristic curve for tau (0.82) was significantly larger than that for 14-3-3 protein (0.68) (p < 0.001). Diagnostic test statistics are provided for the study subjects with 58.3% prevalence, and for a more typical, nonselected, 7.5% prevalence as received by our center.
In this study, tau is superior to 14-3-3 protein as a marker in the diagnosis of Creutzfeldt-Jakob disease, and is as efficient singly compared to a variety of combinations with 14-3-3 protein. This is the first study of this magnitude to examine prion disease diagnostic tests in a carefully characterized patient population with detailed statistical evaluation.

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Available from: Douglas Yates Rowland, Aug 05, 2014
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    • "Hamlin et al. have recently reported that determination of tau protein might be preferable to 14-3-3, as its specificity was found to be significantly higher (67% versus 40%). The sensitivity found was slightly lower than that of 14-3-3 (90% versus 87%) [7]. Other researchers have also reported a higher sensitivity of tau protein (95.2% versus 76.2%) in the early diagnostics of CJD [8]. "
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    ABSTRACT: Objective. Several tests are available in the diagnostics of sporadic Creutzfeldt-Jakob disease (sCJD); however, none of these is conclusive. We review the values of these tests, from an intensive care unit (ICU) perspective. Methods. Case report and review of the literature. Results. A 53-year-old woman initially presenting with psychiatric symptoms developed myoclonus and was admitted 1 month later to the ICU with a suspected nonconvulsive status epilepticus and respiratory insufficiency, probably due to extensive antiepileptic drug therapy. Typical MRI and EEG findings and a positive 14-3-3 protein led to the diagnosis of sCJD. All treatments were terminated, and autopsy confirmed sCJD. Conclusions. Clinical signs combined with MRI, EEG, and 14-3-3 and/or tau protein determination might be sufficient to diagnose or exclude sCJD and may therefore prevent the application of unnecessary diagnostic tests.
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