Raised CSF phospho-tau concentrations in variant Creutzfeldt-Jakob disease: diagnostic and pathological implications.
OBJECTIVE
To investigate whether phosphorylated tau protein (tau-pT181) is increased in variant Creutzfeldt-Jakob disease (vCJD) and if the tau-pT181/tau protein ratio is useful for distinguishing between patients with and without CJD.


METHODS
CSF tau protein and tau-pT181 were measured in 50 patients with sporadic CJD (sCJD), 51 patients with vCJD, 46 sCJD controls, and 37 vCJD controls, using Innotest hTau and Innotest P-Thr181, Innogenetics.


RESULTS
Concentrations of CSF tau protein were increased in sCJD (5120 v 367 pg/ml in controls, p < 0.001) and vCJD (952 v 106 pg/ml, p < 0.001); tau-pT181 was also raised in sCJD (61 v 35 pg/ml in controls, p = 0.002) and vCJD (114 v 33 pg/ml, p < 0.001). Median concentrations of tau-pT181 were higher in vCJD than in sCJD (p < 0.001). The tau-pT181/tau protein ratio was lower than in controls in both sCJD (12 v 128 (p < 0.001)) and vCJD (119 v 279 (p < 0.001)). Mean tau-pT181/tau protein ratio was 10-fold higher in vCJD than in sCJD. Raised CSF tau protein had the highest efficiency for distinguishing sCJD and vCJD from controls.


CONCLUSIONS
CSF tau-pT181 concentrations are raised in vCJD and are higher than in sCJD. Measurement of CSF tau-pT181/tau protein ratio does not improve the diagnostic efficiency of CSF tau protein alone for either vCJD or sCJD. The higher concentration of CSF tau-pT181 found in vCJD suggests that unexplained pathogenic factors influence the phosphorylation of tau protein in vCJD patients.
Goodall
C A
CA
The National Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh, UK.
Head
M W
MW
Everington
D
D
Ironside
J W
JW
Knight
R S G
RS
Green
A J E
AJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D016875:tau Proteins