Desmoplakin as a potential candidate for cerebrospinal fluid marker to rule out 14-3-3 false positive rates in sporadic Creutzfeldt-Jakob disease differential diagnosis.
BACKGROUND
The detection of a 14-3-3 elevated level in cerebrospinal fluid (CSF) is a part of the diagnostic criteria for probable sporadic Creutzfeldt-Jakob disease (sCJD), as defined by the WHO. However, some pathological conditions associated with acute neuronal damage may result in a positive 14-3-3 test and thereby reduce test specificity in sCJD.


OBJECTIVE
Desmoplakin has been previously identified as up-regulated CSF protein in sCJD and these studies aimed to investigate its diagnostic utility and compare it with two known CSF markers, 14-3-3 and tau.


RESULTS
We tested CSF levels of 14-3-3, tau and desmoplakin in 58 sCJD patients and 81 control patients including 45 cases with an elevated 14-3-3 level due to other disease than sCJD. We detected an elevated CSF level of desmoplakin in 78% of the sCJD patients, while 14-3-3 (88%) and tau (91%) showed a higher positive rate. However, the false positive rate of newly tested desmoplakin was significantly lower in comparison to 14-3-3 and tau, and it accounted for only 11% versus 56% and 35%, respectively. Further reduction of false positive rates was achieved by combination of elevated tau level with a positive desmoplakin test. Moreover, in the non-sCJD group, desmoplakin level did not correlate with the level of both above-mentioned CSF markers, whereas a clear correlation was observed in the sCJD group.


CONCLUSIONS
Desmoplakin showed a low positive rate accompanied by a very low false positive rate. Thus, we conclude that desmoplakin is a promising candidate for supportive CSF marker to rule out 14-3-3 false positive cases in sCJD differential diagnosis.
National Reference Center for TSE Surveillance, Department of Neurology, Medical Center Georg August University, Göttingen, Germany. epicjd@med.uni-goettingen.de
Joanna
J
Gawinecka
Barbara
B
Ciesielczyk
Pascual
P
Sanchez-Juan
Matthias
M
Schmitz
Uta
U
Heinemann
Inga
I
Zerr
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D051180:Desmoplakins / Q000134:cerebrospinal fluid*; D003937:Diagnosis, Differential; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016875:tau Proteins / Q000134:cerebrospinal fluid
D048948:14-3-3 Proteins; D015415:Biomarkers; D051180:Desmoplakins; D016875:tau Proteins