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Raised CSF phospho-tau concentrations in variant Creutzfeldt–Jakob disease: diagnostic and pathological implications
  1. C A Goodall,
  2. M W Head,
  3. D Everington,
  4. J W Ironside,
  5. R S G Knight,
  6. A J E Green
  1. The National Creutzfeldt–Jakob Disease Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh, UK
  1. Correspondence to:
 Dr Alison Green
 The National CJD Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK; Alison.Green{at}ed.ac.uk

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 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.

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Footnotes

  • Competing interests: none declared

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