Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt–Jakob disease

Büerger, Katharina; Otto, Markus; Teipel, Stefan J.; Zinkowski, Raymond; Blennow, Kaj; DeBernardis, John F.; Kerkman, Daniel J.; Schröder, Johannes; Schönknecht, Peter; Cepek, Lukas; McCulloch, Cheryl; Möller, Hans‐Jürgen; Wiltfang, Jens; Kretzschmar, Hans A.; Hampel, Harald

doi:10.1016/j.neurobiolaging.2004.12.003

Cited by 67 publications

(48 citation statements)

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“…The extremely high levels of t-tau that we found in sCJD patients are in accordance with other studies [5,14,22,28,32,38,39], with sensitivity (87-94%) and specificity (90-100%) figures similar to ours. In fact, t-tau has been suggested to be the most sensitive marker in early stage sCJD [33].…”

Section: Discussionsupporting

confidence: 93%

“…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%

“…Unlike what happens in Alzheimer's disease (AD), hyperphosphorylation of tau and formation of neurofibrillary tangles (NFTs) do not occur in sCJD. As so the ratio between phosphorylated tau (p-tau) and t-tau levels (p-tau/ t-tau) was shown to improve discrimination between AD and sCJD, with lower levels in favour of the latter [5,28,32]. Reduced Ab42 CSF levels have also been reported in sCJD patients, as in AD, but mostly overlapping [17,38,39].…”

Section: Introductionmentioning

confidence: 92%

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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: 93%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 92%

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

et al. 2009

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“…It is believed that deregulated tau may be reflecting the neuronal and axonal damage present in brain tissue and, as a consequence, the presence of increased tau levels is not a specific event for AD. Accordingly, transient tau increments have been also reported in acute stroke [123], and the most increased tau levels are observed in prion diseases such as in CJD, where massive neuronal cell death is present [124,125]. Higher CSF tau is also associated with smaller brain volume in individuals with AD [126].…”

Section: Taumentioning

confidence: 99%

New Frontiers in Alzheimer's Disease Diagnosis

Llorens¹,

Nuhn²,

Peter³

et al. 2015

Alzheimer's Disease - Challenges for the Future

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“…However, the ratio between p-Tau and t-Tau levels (p-Tau/t-Tau) has shown to improve discrimination between AD or other RPDs and sCJD, with lower levels in favour of the latter [14,24,29,30]. Only limited information is available on p-Tau/t-Tau ratio optimal cutoff levels and its comparative value in relation to 14-3-3 or t-Tau alone [31].…”

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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Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt–Jakob disease

Cited by 67 publications

References 23 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

New Frontiers in Alzheimer's Disease Diagnosis

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

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