14-3-3 testing in diagnosing Creutzfeldt–Jakob disease

Lemstra, Afina W.; Meegen, M. T. van; Vreyling, J. P.; Meijerink, P.H.S.; Jansen, Gerard H.; Bulk, Saskia; Baas, Frank; Gool, Willem A. van

doi:10.1212/wnl.55.4.514

Cited by 113 publications

(73 citation statements)

References 19 publications

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“…Immunodetection of protein 14-3-3 in CSF was originally demonstrated to have a high sensitivity and specificity for sCJD [19,42] and has, therefore, been included by the World Health Organization (WHO) in the diagnostic criteria for probable disease [41]. However, this view has been challenged by findings of poor specificity [6,7] and low sensitivity in autopsy-proven sCJD cases [11].…”

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 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: Introductionmentioning

confidence: 99%

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

et al. 2009

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“…The positive ratio of 14-3-3 protein is generally high in CJD, but this protein does not seem to be a highly specific marker (Lemstra et al 2000;Huang et al 2003). There are other reports that the 14-3-3 protein ratio is also elevated in cases of cerebral vessel disorder, brain fever, meningitis, metabolic encephalopathy, low-oxygen encephalosis, Hashimoto's encephalopathy, nervous system paraneoplastic disorders, and Alzheimer disease (Saiz et al 1999;Lemstra et al 2000;Huang et al 2003). Bersano et al (2006) reported that a high level of 14-3-3 protein was also observed in Guillain-Barré syndrome, a peripheral nerve disease.…”

Section: Discussionmentioning

confidence: 86%

“…It has been reported that specific proteins in the CSF, such as 14-3-3 protein, tau protein, S-100 protein, and NSE, are useful as diagnostic markers of CJD. 14-3-3 protein may be present in the CSF because of the sudden destruction of cerebral neurocytes (Lemstra et al 2000;Shiga et al 2006), and is used as a diagnostic criterion of CJD (Table 1; Zeidler et al 1998). The positive ratio of 14-3-3 protein is generally high in CJD, but this protein does not seem to be a highly specific marker (Lemstra et al 2000;Huang et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…14-3-3 protein may be present in the CSF because of the sudden destruction of cerebral neurocytes (Lemstra et al 2000;Shiga et al 2006), and is used as a diagnostic criterion of CJD (Table 1; Zeidler et al 1998). The positive ratio of 14-3-3 protein is generally high in CJD, but this protein does not seem to be a highly specific marker (Lemstra et al 2000;Huang et al 2003). There are other reports that the 14-3-3 protein ratio is also elevated in cases of cerebral vessel disorder, brain fever, meningitis, metabolic encephalopathy, low-oxygen encephalosis, Hashimoto's encephalopathy, nervous system paraneoplastic disorders, and Alzheimer disease (Saiz et al 1999;Lemstra et al 2000;Huang et al 2003).…”

Section: Discussionmentioning

confidence: 99%

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Creutzfeldt-Jakob Disease with Paralysis of the Unilateral Vocal Cord and Soft Palate

Hasegawa

Okumura

Osumi

et al. 2011

Tohoku J. Exp. Med.

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“…Immunodetection of protein 14-3-3 in CSF was originally demonstrated to have a high sensitivity and specificity for sCJD [8,9]. International collaborative studies [10], as well as single center studies [11][12][13][14], have shown that in the appropriate clinical circumstances, a positive 14-3-3 protein detection correlates with clinical diagnosis in 85-94 % of cases.…”

Section: Introductionmentioning

confidence: 99%

CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt–Jakob disease suspected cases with inconclusive 14-3-3 result

et al. 2016

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Cerebrospinal fluid (CSF) 14-3-3 protein supports sporadic Creutzfeldt-Jakob (sCJD) diagnosis, but often leads to weak-positive results and lacks standardization. In this study, we explored the added diagnostic value of Total Tau (t-Tau) and phosphorylated Tau (p-Tau) in sCJD diagnosis, particularly in the cases with inconclusive 14-3-3 result. 95 definite sCJD and 287 patients without prion disease (non-CJD) were included in this study. CSF samples were collected in routine clinical diagnosis and analysed for 14-3-3 detection by Western blot (WB). CSF t-Tau and p-Tau were quantified by commercial ELISA kits and PRNP and APOE genotyping assessed by PCR-RFLP. In a regression analysis of the whole cohort, 14-3-3 protein revealed an overall accuracy of 82 % (sensitivity = 96.7 %; specificity = 75.6 %) for sCJD. Regarding 14-3-3 clear positive results, we observed no added value either of t-Tau alone or p-Tau/t-Tau ratio in the model. On the other hand, considering 14-3-3 weakpositive cases, t-Tau protein increased the overall accuracy of 14-3-3 alone from 91 to 94 % and specificity from 74 to 93 % (p \ 0.05), with no sensitivity improvement. However, inclusion of p-Tau/t-Tau ratio did not significantly improve the first model (p = 0.0595). Globally, t-Tau protein allowed a further discrimination of 65 % within 14-3-3 inconclusive results. Furthermore, PRNP MV genotype showed a trend to decrease 14-3-3 sensitivity (p = 0.051), but such effect was not seen on t-Tau protein.In light of these results, we suggest that t-Tau protein assay is of significant importance as a second marker in identifying 14-3-3 false-positive results among sCJD probable cases.

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14-3-3 testing in diagnosing Creutzfeldt–Jakob disease

Abstract: The 14-3-3 protein is a highly sensitive and specific marker for CJD when used in the appropriate clinical context.

Cited by 113 publications

References 19 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

Creutzfeldt-Jakob Disease with Paralysis of the Unilateral Vocal Cord and Soft Palate

CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt–Jakob disease suspected cases with inconclusive 14-3-3 result

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