Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease

Karch, André; Hermann, Péter; Ponto, Claudia; Schmitz, Matthias; Arora, Amandeep Singh; Zafar, Saima; Llorens, Franc; Müller-Heine, A.; Zerr, Inga

doi:10.1016/j.neurobiolaging.2015.01.021

Cited by 34 publications

(35 citation statements)

References 12 publications

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“…On the contrary, the sensitivity of t-Tau towards sCJD remained unchanged by these patient characteristics. Despite the fact that the relatively small number of patients might limit the conclusions taken from this analysis, these are in general agreement with the results from large population studies [50,53]. This difference in the protein markers sensitivity between sCJD sub-types might be accounted by the modulation of clinical phenotype by molecular characteristics.…”

Section: Discussionsupporting

confidence: 86%

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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Section: Discussionsupporting

confidence: 86%

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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“…For instance, we recently reported that CSF tau is a marker for the molecular type in sCJD, which might, among others, reflect different intensities of neuronal damage [19,20]. Differences of tau levels dependent on patient characteristics might have led to the heterogeneity in diagnostic accuracy measures reported for tau.…”

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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“…Total tau protein can be used as a diagnostic test for the assessment of PRNP when the codon 129 genotype is known (26), while the marker is not CJD-specific and can also be detected in numerous other diseases. Certain studies have shown that the sensitivity of 14-3-3 protein for detecting CJD varies for different CJD genotypes: From 57% in MV2 to 100% in MV1 and VV1 cases, with a specificity from 84 to 95% (27,28).…”

Section: Discussionmentioning

confidence: 99%

Three sporadic cases of Creutzfeldt-Jakob disease in China and their clinical analysis

Wang

Liu

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The present study described the characteristics of three cases of Creutzfeldt-Jakob disease (CJD) in China and analyzed their clinical presentations. The clinical information of the three cases was collected and analyzed. Blood and cerebrospinal fluid (CSF) specimens of the patients were collected for detection of the prion protein (PRNP) gene and 14-3-3 protein levels. Dynamic changes of electroencephalograms (EEGs) and brain magnetic resonance images (MRIs) were also observed. All the three cases were sporadic CJD cases. They presented with symptoms including hyposthenia, progressive memory loss, truncal and limb ataxia, dysarthria, lowered vision acuity, bucking, language disorders, myoclonia and akinetic mutism state. One of the three cases was associated with a prolonged duration of >6 years. The EEG of two cases showed slow biphasic waves. The diffusion-weighted MRI sequence revealed abnormal hyperintensity and bilateral ribboning in the cortex. Two patients tested positive for the 14-3-3 protein in the CSF. All patients were of methionine homozygosity at codon 129 in the gene encoding PRNP protein and one patient had a mutation. The CJD cases showed differences in terms of symptoms and disease duration. Subacute onset was common and with attentive nursing and supportive treatments, one of the patients had a prolonged survival time of >6 years. IntroductionCreutzfeldt-Jakob disease (CJD) is a progressive neurodegenerative disorder that is caused by prion protein deposition in the central nervous system. As the most common type of human transmissible spongiform encephalopathy, CJD is incurable and fatal with a duration from a few months to two years (1). Typical CJD triad symptoms include progressive dementia, myoclonus and electroencephalographic (EEG) changes (periodic triphasic sharp wave complexes) (2). Traditionally, CJD is classified as sporadic (sCJD), familial (fCJD), iatrogenic (iCJD) and variant CJD (vCJD) (3). Different subtypes are associated with specific clinical symptoms and pathological features (4,5). sCJD, accounting for ~85% of all cases worldwide, is categorized into six subtypes according to the methionine (M)/valine (V) polymorphism at codon 129 of the PRNP gene (6,7). fCJD accounts for 5-10% of all cases and is an autosomal dominant disorder associated with various mutations of the PRNP gene (8,9). The main causes of iCJD include contaminated human hormone supplements, corneal transplantation and transplantation of cadaveric dura mater (10). At present, vCJD, which is transmitted from cows with bovine spongiform encephalopathy to humans, mainly affects younger adults in Europe with different clinical, etiological and neuropathological features as well as risk factors compared with other types of CJD (11-13).Although final diagnosis of CJD requires neuropathological biopsy examination of affected brain tissues, nonpathological methods are currently used worldwide for the early diagnosis and prevention of CJD (14). At present, the diagnosis of CJD is frequently delayed or CJD ...

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Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease

Cited by 34 publications

References 12 publications

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

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

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

Three sporadic cases of Creutzfeldt-Jakob disease in China and their clinical analysis

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