Use of 14-3-3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt-Jakob disease

Green, A J E; Thompson, E. J.; Stewart, G.; Zeidler, Martin; McKenzie, J. M.; Macleod, Margaret-Ann; Ironside, James W.; Will, R. G.; Knight, Richard

doi:10.1136/jnnp.70.6.744

Cited by 143 publications

(87 citation statements)

References 32 publications

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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%

“…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]. Using a commercial ELISA test for S-100b, we have reached a sensitivity and specificity of 93%, both higher than those reported using either an in-house ELISA or a different commercial kit [21,30,43].…”

Section: Discussionsupporting

confidence: 91%

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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%

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

et al. 2009

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“…Patients with a clinical picture indicative of "possible" disease could be considered "probable" cases of Creutzfeldt-Jacob disease if there is an association of high CSF levels of NSE and 14-3-3 protein (19). In the variant form of CreutzfeldtJacob disease, it has been shown that cNSE is less sensitive as an indicator, probably because of the slower progression of the variant form (20).…”

Section: Introductionmentioning

confidence: 99%

Use of neuron-specific enolase for assessing the severity and outcome of neurological disorders in patients

Lima

Takayanagui

Garcia

et al. 2004

Braz J Med Biol Res

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Neuron-specific enolase (NSE) is a glycolytic enzyme present almost exclusively in neurons and neuroendocrine cells. NSE levels in cerebrospinal fluid (CSF) are assumed to be useful to estimate neuronal injury and clinical outcome of patients with serious clinical manifestations such as those observed in stroke, head injury, anoxic encephalopathy, encephalitis, brain metastasis, and status epilepticus. We compared levels of NSE in serum (sNSE) and in CSF (cNSE) among four groups: patients with meningitis (N = 11), patients with encephalic injuries associated with impairment of consciousness (ENC, N = 7), patients with neurocysticercosis (N = 25), and normal subjects (N = 8). Albumin was determined in serum and CSF samples, and the albumin quotient was used to estimate blood-brain barrier permeability. The Glasgow Coma Scale score was calculated at the time of lumbar puncture and the Glasgow Outcome Scale (GOS) score was calculated at the time of patient discharge or death. The ENC group had significantly higher cNSE (P = 0.01) and albumin quotient (P = 0.005), but not sNSE (P = 0.14), levels than the other groups (KruskalWallis test). Patients with lower GOS scores had higher cNSE levels (P = 0.035) than patients with favorable outcomes. Our findings indicate that sNSE is not sensitive enough to detect neuronal damage, but cNSE seems to be reliable for assessing patients with considerable neurological insult and cases with adverse outcome. However, one should be cautious about estimating the severity of neurological status as well as outcome based exclusively on cNSE in a single patient.

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“…Several studies have reported increased abundances of S100B in CSF from patients afflicted with sporadic and variant CJD [7,40,74] and preclinical Alzheimer's disease (AD) [73]. In cattle CSF, S100B levels were significantly elevated in confirmed field cases of BSE when compared to clinically normal controls and to BSE-suspect animals later confirmed as BSE negative by histopathology [39].…”

Section: S100b Proteins and Glial Fibrilliary Acidic Proteinsmentioning

confidence: 99%

“…In addition, Tau protein analysis may be useful for diagnosis of other human TSEs. Concentrations of total Tau protein are often elevated in CSF from patients with vCJD [40] and some research suggests that dementia specific changes in Tau protein phosphorylation have been observed [51,114].…”

Section: Tau Proteinsmentioning

confidence: 99%

The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal

Parveen

Moorby²,

Allison³

et al. 2005

Vet. Res.

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-Scrapie and bovine spongiform encephalopathy (BSE) are major global concerns and the emergence of variant Creutzfeldt-Jakob disease (vCJD) has caused turmoil for blood transfusion services and hospitals worldwide. Recent reports of iatrogenic CJD (iCJD) cases following blood transfusions from Transmissible Spongiform Encephalopathies (TSE)-infected donors have fuelled this concern. Major diagnostic tests for BSE and scrapie are conducted post-mortem from animals in late stages of the disease. Although the lymphoreticular system is involved in the earlier pathogenesis of some forms of sheep scrapie and vCJD, which presents great opportunity for diagnostic development, other TSE diseases (some strains of scrapie, sporadic CJD (sCJD) and bovine BSE) do not present such a diagnostic opportunity. Thus, there is an urgent need for premortem tests that differentiate between healthy and diseased individuals at early stages of illness, in accessible samples such as blood and urine using less invasive procedures. This review reports on the current state of progress in the development and use of prion and non-prion biomarkers in the diagnosis of TSE diseases. Some of these efforts have concentrated on improving the sensitivity of PrP Sc detection to allow in vivo diagnosis at low abundances of PrP Sc whilst others have sought to identify non-prion protein biomarkers of TSE disease, many of which are still at early stages of development. In this review we comment upon the limitations of prion based tests and review current research on the development of tests for TSE that rely on non-prion disease markers in body fluids that may allow preclinical disease diagnosis.

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Use of 14-3-3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt-Jakob disease

Cited by 143 publications

References 32 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

Use of neuron-specific enolase for assessing the severity and outcome of neurological disorders in patients

The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal

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