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. 2008 Aug 27:5:14.
doi: 10.1186/1743-8454-5-14.

Cerebrospinal fluid markers in Creutzfeldt-Jakob disease

Anders Skinningsrud  1 , Vidar Stenset, Astrid S Gundersen, Tormod Fladby
Affiliations

Cerebrospinal fluid markers in Creutzfeldt-Jakob disease

Anders Skinningsrud et al. Cerebrospinal Fluid Res. .

Abstract

Background: The objective was to assess the utility of total tau protein (tTau), the ratio of (tTau)/181 phosphorylated tau protein (P-Tau) and 14-3-3 protein, as diagnostic markers in cerebrospinal fluid (CSF) for Creutzfeldt-Jakob disease (CJD).

Methods: CSF samples received from Norwegian hospitals between August 2005 and August 2007 were retrospectively selected from consecutive patients with tTau values > 1200 ng/L (n = 38). The samples from patients clinically diagnosed with CJD (n = 12) were compared to those from patients with other degenerative neurological diseases: Alzheimer's/vascular dementia (AD/VaD, n = 21), other neurological diseases (OND, n = 5). Total Tau, P-Tau, and beta-Amyloid (Abeta42) were measured with commercial kits. Additionally, 14-3-3 protein was measured semi-quantitatively by immunoblot.

Results: The minimum cut-off limits for diagnosis of CJD were chosen from the test results. For tTau the lower limit was fixed at 3000 ng/L, for the tTau/P-Tau ratio it was 60, and for 14-3-3 protein it was 0.75 arbitrary units. For tTau and tTau/P-Tau ratio, all but three CJD patients had levels above the minimum, whereas almost all of the other patients were below. For the 14-3-3 protein, two CJD patients were below the minimum and five were above. Only one of the other patients was higher than the limit. The sensitivities, specificities and diagnostic efficiencies were: tTau 75%, 92%, and 87%; tTau/P-Tau 75%, 96%, and 89%; and 14-3-3 protein 80%, 96%, and 91%.

Conclusion: The results suggest that 14-3-3 protein may be the better marker for CJD, tTau/P-Tau ratio and tTau are also efficient markers, but showed slightly inferior diagnostic properties in this study, with tTau/P-Tau marginally better than tTau.

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Figures

Figure 1
Figure 1
Data plots of Tau protein (tTau) (A) and tTau/P-Tau ratio (B) by diagnostic group Creutzfeldt-Jakob disease (CJD), other neurological diseases (OND) and Alzheimer's disease or vascular dementia (AD/VaD). Horizontal dashed lines show chosen lower limit for CJD: tTau: 3000 ng/L, and tTau/P-Tau ratio: 60.
Figure 2
Figure 2
Data plots of 181-phosphorylated tau protein (P-Tau) (A) and beta-amyloid (Aβ42) (B) by diagnostic group CJD, OND and AD/VaD with upper (P-Tau) and lower (Aβ42) normal limits used in clinical practice (dashed lines): P-Tau: 80 ng/L, Aβ42: 550 ng/L.
Figure 3
Figure 3
Data plots of 14-3-3 protein by diagnostic group CJD, OND and AD/VaD with lower limit for CJD (dashed line): 0.75 arbitrary units (data from Akershus University Hospital only).
See this image and copyright information in PMC

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