Phosphorylated tau in cerebrospinal fluid as a marker for Creutzfeldt-Jakob disease.
OBJECTIVE
To determine the concentrations of microtubule associated protein tau and multiple phosphorylated tau epitopes in the cerebrospinal fluid of patients with sporadic Creutzfeldt-Jakob disease (sCJD), dementias, and controls, in order to evaluate their diagnostic use and clinical relevance.


METHODS
The CSF concentrations of total tau and phosphorylated tau at epitope 181 were determined by enzyme linked immunosorbent assay in 66 definite and nine probable sCJD patients, and in 97 controls. Other phosphorylated tau epitopes were investigated by western blot.


RESULTS
In the sCJD population, determination of 14-3-3 protein and total tau protein concentrations was of the highest diagnostic value, with a sensitivity of 96% and 92%, respectively, and a specificity of 94% and 97%. Two distinct subgroups could be identified among the 75 sCJD patients based on the detection of phosphorylated tau at threonine 181 and serines 199, 202, and 404. A high phosphorylated tau concentration was clinically correlated with a significantly shorter disease duration, early onset of akinetic mutism, and a higher rate of typical EEGs (p < 0.05).


CONCLUSIONS
Although the determination of phosphorylated tau levels cannot be used as a diagnostic biomarker, it may prove useful for estimating the prognosis of an sCJD patient. These experiments reconfirm that sCJD is a disease with a complex pathology.
Van Everbroeck
B
B
Laboratory of Neurobiology and Neuropathology, Born Bunge Foundation, University of Antwerp, Wilrijk, Belgium.
Green
A J E
AJ
Vanmechelen
E
E
Vanderstichele
H
H
Pals
P
P
Sanchez-Valle
R
R
Corrales
N Cuadrado
NC
Martin
J-J
JJ
Cras
P
P
D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011237:Predictive Value of Tests; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism
D015415:Biomarkers; D016875:tau Proteins