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From the Neurologische Klinik und Poliklinik (Drs. Otto, Cepek, Mollenhauer, Steinacker, and Poser, and B. Ciesielczyk), Psychiatrische Klinik und Poliklinik (Dr. Wiltfang), and Institut für Neuropathologie (Dr. Schulz–Schaeffer), Georg-August-Universität Göttingen, and Institut für Neuropathologie (Drs. Neumann and Kretzschmar), Ludwig Maximilian Universität, Munich, Germany.
Address correspondence and reprint requests to Dr. Markus Otto, Neurologische Klinik und Poliklinik, Universität Göttingen, Robert-Koch Str. 40, 37070 Göttingen, Germany; e-mail: motto{at}gwdg.de
Background: Diagnosis of Creutzfeldt–Jakob disease (CJD) is made according to the typical clinical picture and can be supported by a positive 14-3-3 CSF immunoblot. Promising results for the diagnostic sensitivity and specificity of tau-protein measurement in CSF already have been described in a smaller group of patients. Both tests in a larger group of patients with the differential diagnosis of CJD were evaluated.
Methods: CSF of 297 patients under the differential diagnosis of CJD (109 definite, 55 probable, 39 possible; 85 others, 1 iatrogenic, 8 genetic), 23 nondemented control subjects, and 15 non-CJD patients with positive 14-3-3 immunoblots were analyzed. The 14-3-3 immunoblot bands were semiquantitatively rated as strong, medium, and weak. Tau-protein was analyzed using a commercially available ELISA. In addition, patients were neuropathologically classified according to prion protein type and polymorphism at codon 129.
Results: A diagnostic sensitivity of 94%, a diagnostic specificity of 90%, and a positive predictive value of 92% were achieved for tau-protein at a cut-off of 1,300 pg/mL. These results are comparable with those of the 14-3-3 immunoblot. For patients with type II prion protein and methionine/valine or valine/valine polymorphism at codon 129, tau-protein has a higher diagnostic sensitivity than 14-3-3 protein. Tau-protein levels were significantly higher in patients with higher-rated 14-3-3 immunoblot bands.
Conclusion: The differential diagnostic significance of the 14-3-3 immunoblot is similar to that of the tau-protein ELISA. The advantage of the tau-protein ELISA is that it is easy to use in routine laboratories. Patients with a negative 14-3-3 immunoblot already have measurable tau-protein levels. This increases information on 14-3-3—negative patients with CJD and especially on patients with other diseases.
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