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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    • "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.
    04/2013; 2013:630141. DOI:10.1155/2013/630141
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    ABSTRACT: Creutzfeldt-Jakob disease (CJD) has an annual incidence of 1 per million persons. With ∼300 US cases per year, and over 15,000 neurologists, we see a patient with CJD, by chance, once in 50 years of clinical practice. How does the accuracy of CSF tau vs 14-3-3 protein affect clinical diagnosis?
    Neurology 07/2012; 79(6):551. DOI:10.1212/WNL.0b013e3182635834 · 8.29 Impact Factor
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    ABSTRACT: Rapidly progressive dementia (RPD) is a rare presentation of different neurological disorders characterized by cognitive impairment leading to loss of functional independence within 24 months or less. The increasing recognition of treatable non-prion causes of RPD has made the differential diagnosis with sporadic Creutzfeldt-Jakob disease (sCJD) of crucial importance. We therefore assessed the frequency of different etiologies of RPD and evaluated the accuracy of newly proposed diagnostic criteria for sCJD. Clinical records of patients with RPD referred to Memory Clinic between 2007 and 2012 were retrospectively analyzed. The accuracy of diagnostic criteria for sCJD was evaluated by: a) MRI images in DWI and FLAIR sequences; and (b) CSF 14-3-3 protein. In addition, CSF total tau protein level was also assessed. Final diagnosis was obtained after a 1-year follow-up or after autopsy. Among 37 patients with RPD, the most frequent causes were non-prion diseases, either untreatable (38%) or potentially treatable (32%), thus leaving sCJD as a less frequent cause (30%). DWI images had a sensitivity of 73% and specificity of 96%, while FLAIR yielded a very low sensitivity (40%). CSF 14-3-3 protein had a sensitivity of 100%, but a very low specificity (43%). The strongest independent predictor of sCJD diagnosis was the CSF tau level (p = 0.002) (91% sensitivity, 83% specificity). Treatable causes of RPD are as frequent as sCJD and a rapid differential diagnosis is mandatory. We suggest that DWI images and CSF analysis combining 14-3-3 and total tau protein determination hold the best informative diagnostic values.
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