Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease.
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.


CONCLUSIONS
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.
Otto
M
M
Neurologische Klinik und Poliklinik, Georg-August-Universität Göttingen, Germany. motto@gwdg.de
Wiltfang
J
J
Cepek
L
L
Neumann
M
M
Mollenhauer
B
B
Steinacker
P
P
Ciesielczyk
B
B
Schulz-Schaeffer
W
W
Kretzschmar
H A
HA
Poser
S
S
D048948:14-3-3 Proteins; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D003704:Dementia / Q000209:etiology / Q000503:physiopathology; D003937:Diagnosis, Differential; D004791:Enzyme Inhibitors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D014446:Tyrosine 3-Monooxygenase / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D048948:14-3-3 Proteins; D004791:Enzyme Inhibitors; D016875:tau Proteins; D014446:Tyrosine 3-Monooxygenase