Raised CSF phospho-tau concentrations in variant Creutzfeldt-Jakob disease: diagnostic and pathological implications

Abstract

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 taupT181/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 taupT181/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.

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

“…Similar results were found with P-tau 231 /T-tau (Buerger, Otto et al 2006). It is important to note that CSF P-tau 181 level in new variant CJD are higher than in sporadic CJD, and this inversely to T-tau CSF level (Goodall, Head et al 2006). So, this ratio P-tau 181 /T-tau is able to differentiate sporadic CJD from new variant with an elevated ratio.…”

Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients

“…CSF Ab42, t-tau and p-tau-181 were measured by commercially available sandwich ELISA kits (Innotest, Innogenetics, Ghent, Belgium), according to the manufacturer instructions, as previously reported [12,17] CSF S-100b was measured by a commercially ELISA kit (Sangtec 100 ELISA, DiaSorin, Stillwater, MN, USA), according to the manufacturer instructions. All assays were performed sequentially in a clinical routine setting.…”

“…In a clinical setting, putative CSF markers would be most useful in identifying sCJD cases in a cohort of mixed pathologies with a similar presentation of rapidly progressive dementia and therefore suspected to have sCJD. A few studies have addressed this problem [2,12,39] with some limitations, either enrolling a very limited number of patients, or assessing only two or three different CSF markers.…”

Tau as a Biomarker of Neurodegenerative Diseases

“…Using a cut-off value of 1300 pg/ml, several studies on the differentiation of CJD from AD and other dementia showed that CSF-tTau level is a highly discriminative marker, which has recently been confirmed in a neuropathological study to be as good as the established 14-3-3 marker for CJD [103]. Elevated values for CSF-tTau have also been found in a bovine variant of CJD [104]. Increases of CSF-tTau levels are observed in several other acute neurological conditions, such as severe malaria [105], Wernicke's encephalopathy [106], pediatric patients with brain tumor, hydrocephalus or serious CNS infections [107].…”