Diagnostic value of 14-3-3β immunoblot and T-tau/P-tau ratio in clinically suspected Creutzfeldt-Jakob disease

Blennow, Kaj; Johansson, Annica; Zetterberg, Henrik

doi:10.3892/ijmm.16.6.1147

Cited by 35 publications

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“…Furthermore, associating ttau with p-tau (p-tau/t-tau ratio) improved the sensitivity of the t-tau test alone (from 90% to 93%), but not its specificity (95%). This is in line with previous studies, reporting comparable sensitivity (78-100%) and specificity (93-100%) [2,5,28,32]. The increase in CSF S-100b levels observed in sCJD patients has been previously reported, but the absolute values are difficult to compare as different methodologies have been employed [14,30,31].…”

Section: Discussionsupporting

confidence: 91%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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The clinical diagnosis of sporadic CreutzfeldtJakob disease (sCJD) is difficult, and reliable markers are highly desired. In this work we assess the value of several cerebrospinal fluid (CSF) markers for sCJD diagnosis. Within the framework of the Portuguese Epidemiological Surveillance Program for Human Prion Diseases, CSF samples from 71 patients with clinically suspected sCJD, 30 definite sCJD and 41 non-CJD patients, were analysed for the presence of 14-3-3 protein. CSF levels of tau (t-tau), and phosphorylated tau (p-tau181), S-100b and b amyloid (Ab42) proteins were determined. The influence of clinical and genetic characteristics on CSF markers sensitivity was also evaluated. Protein 14-3-3 was detected in 29/30 sCJD patients and 9/41 non-CJD patients. Extremely elevated t-tau and S-100b protein levels were found in sCJD patients, while p-tau181 levels were only slightly elevated and Ab42 showed no differences compared to controls. 14-3-3 was the most sensitive parameter (97%), but its specificity was low (78%); sensitivity/specificity for other proteins were: S-100b-93/93%, t-tau-93/95%, with maximum accuracy being obtained by a combination of tests (14-3-3 combined with either t-tau or S-100b, or combining S-100b with t-tau/Ab42 or p-tau/t-tau ratios). The sensitivity of 14-3-3, as well as of p-tau181/t-tau ratio, was decreased in younger patients with long disease duration, with the PrP-2 isotype and MV genotype. Both 14-3-3, t-tau and S-100b are sensitive markers for sCJD, but 14-3-3 specificity seems to be lower in this special clinical setting of rapidly progressing dementias. We propose that in cases with a 14-3-3 weak positive result, or in young patients with long disease duration, a second CSF marker would be valuable for the diagnosis of sCJD.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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“…The authors reported a sensitivity of 44% (95% CI 12-76.9) and specificity of 74% (95% CI 57.5-90.6) when WB analysis for 14-3-3 ␤ isoform was used. 23 Another Class II study, which had an objective of comparing 3 sets of diagnostic criteria (Master's, French, and European) 24 for diagnosing CJD, included 236 autopsied patients who were classified antemortem into 3 case groups: suspected, probable, or possible. Then, on the basis of the autopsy results that were obtained from 61.2% of the cohort, the percentage of definite cases found in each of the groups was used to estimate the percentage of definite cases in the nonautopsied patient group.…”

Section: Description Of the Analytic Processmentioning

confidence: 99%

Evidence-based guideline: Diagnostic accuracy of CSF 14-3-3 protein in sporadic Creutzfeldt-Jakob disease

2012

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Objective: To assess the available evidence for the diagnostic accuracy of CSF testing for protein 14-3-3 in patients with suspected sporadic Creutzfeldt-Jakob disease (sCJD). Methods:The authors performed a systematic review of the available literature from 1995 to January 1, 2011, to identify articles involving patients who were suspected of having sCJD and who had CSF analysis for protein 14-3-3. Studies were rated according to the American Academy of Neurology classification of evidence scheme for diagnostic studies, and recommendations were linked to the strength of the evidence. A pooled estimate of sensitivity and specificity was obtained for all studies rated Class II or higher. The question asked is "Does CSF 14-3-3 protein accurately identify Creutzfeldt-Jakob disease (CJD) in patients with sCJD?" Results:The analysis was conducted on the basis of samples of 1,849 patients with suspected sCJD from 9 Class II studies. Assays for CSF 14-3-3 protein are probably moderately accurate in diagnosing sCJD: sensitivity 92% (95% confidence interval [CI] 89.8-93.6), specificity 80% (95% CI 77.4-83.0), likelihood ratio of 4.7, and negative likelihood ratio of 0.10. Recommendation:For patients who have rapidly progressive dementia and are strongly suspected of having sCJD and for whom diagnosis remains uncertain (pretest probability ϳ20%-90%), clinicians should order CSF 14-3-3 assays to reduce the uncertainty of the diagnosis (Level B). Neurology ® 2012;79:1499-1506 GLOSSARY CI ϭ confidence interval; CJD ϭ Creutzfeldt-Jakob disease; DWI ϭ diffusion-weighted imaging; FLAIR ϭ fluid-attenuated inversion recovery; NSE ϭ neuron-specific enolase; PSWC ϭ periodic sharp and slow wave complexes; ROC ϭ receiver operator characteristic; sCJD ϭ sporadic Creutzfeldt-Jakob disease; WB ϭ Western blot.

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“…14-3-3 is part of the diagnostic criteria for sCJD; however, there is a debate about if the diagnostic accuracy of 14-3-3 is lower [4,5], similar to that of the tau protein [6,7], or even higher [8]. Although elevated tau levels can also be detected in other neurological and neurodegenerative conditions [9,10], an optimum cutoff for the diagnosis of sCJD has been defined in the range of 1,200-1,300 pg/mL [6,11,12,13]. Elevated p-tau levels have also been detected in the CSF of sCJD cases [14], still its clinical value is limited due to its modest increase and the presence of elevated p-tau levels in other neurological and neurodegenerative conditions [9,15].…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Biomarker-Based Diagnosis of Sporadic Creutzfeldt-Jakob Disease: A Validation Study for Previously Established Cutoffs

Llorens

Karch

Golanska

et al. 2017

Dement Geriatr Cogn Disord

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Background: Several biomarkers have been proposed to discriminate sporadic Creutzfeldt-Jakob disease (sCJD) from other dementias and control cases. However, their clinical accuracy depends on the PRNP codon 129 genotype, leaving it unclear how well established markers behave in untested conditions. Methods: We analyzed 14-3-3, tau, p-tau levels, and the p-tau/tau ratio in a population sample collected from Polish hospitals including nondementia, dementia, and definite sCJD cases and validated their parameters according to previously established cutoffs. Additionally, the correlation between biomarkers and disease duration as well as the influence of the PRNP129 polymorphism are reported. Results: The tau levels and p-tau/tau ratios differed considerably between sCJD and clinically characterized non-CJD cases (p < 0.001). p-tau was only elevated in sCJD when compared to cases without dementia (p < 0.05). Tau and the p-tau/tau ratio showed a sensitivity of 95 and 100%, respectively, in detecting sCJD cases. A negative correlation between tau levels and disease duration, but not the timing of lumbar puncture was observed. Conclusion: The present findings confirmed the value of the p-tau/tau ratio as a robust sCJD biomarker and suggest a role for tau as prognostic marker.

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Diagnostic value of 14-3-3β immunoblot and T-tau/P-tau ratio in clinically suspected Creutzfeldt-Jakob disease

Cited by 35 publications

References 0 publications

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

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

Evidence-based guideline: Diagnostic accuracy of CSF 14-3-3 protein in sporadic Creutzfeldt-Jakob disease

Cerebrospinal Fluid Biomarker-Based Diagnosis of Sporadic Creutzfeldt-Jakob Disease: A Validation Study for Previously Established Cutoffs

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