Increased Detection of 14-3-3 Protein in Cerebrospinal Fluid in Sporadic Creutzfeldt-Jakob Disease during the Disease Course

Giraud, P; Biacabe, Anne-Gaëlle; Carrault, Guy; Later, R; Joyeux, O; Moene, Y; Perret‐Liaudet, Armand

doi:10.1159/000066174

Cited by 20 publications

(7 citation statements)

References 10 publications

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“…This observation is in agreement with published single case reports. 10,13,21,37,38 In our analysis, both sensitivity and specificity increased when the results of the second LP were taken into account. The results of a second CSF test might help to exclude CJD, since with time, levels of brain-derived proteins decline in some other conditions, but usually increase further in CJD.…”

Section: Discussionmentioning

confidence: 80%

CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease

Sánchez‐Juan

Green²,

Ladogana³

et al. 2006

Neurology

255

208

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Section: Discussionmentioning

confidence: 80%

CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease

Sánchez‐Juan

Green²,

Ladogana³

et al. 2006

Neurology

255

208

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“…Mollenhauer et al [ 7 ] also discussed the difficulties of CJD diagnosis in advanced cases presenting one sCJD case that became 14-3-3 negative in the final stage of the disease. On the other hand, Giraud et al [ 3 ] reported an increase in the levels of 14-3-3 proteins during the course of the disease in a limited number of sCJD cases. Brandel et al [ 2 ] performed a sequential study in iatrogenic CJD, and observed that 14-3-3 was rarely detectable within the first 3 months of the disease but always positive after 7 months associated with aggravation of the disease and the occurrence of dementia.…”

Section: Discussionmentioning

confidence: 99%

“…Increased levels of other brain-derived proteins, such as microtubule-associated tau protein [ 8 ], S100b [ 4 ] or neurone specific enolase (NSE) [ 13 ] have also been reported to be elevated in CSF in CJD. The published data about how the levels of these proteins are modified during the course of disease are contradictory [ 1 – 3 , 5 – 7 , 10 , 11 ]. In addition, the time point during the disease, when biochemical markers are expected to have the highest sensitivity, is not well-defined.…”

Section: Introductionmentioning

confidence: 99%

Influence of timing on CSF tests value for Creutzfeldt-Jakob disease diagnosis

Sánchez‐Juan

Castilla²,

Green

et al. 2007

J Neurol

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Background The analysis of markers in the cerebrospinal fluid (CSF) is useful in the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). However, the time at which the study of these markers is most sensitive remains controversal. Objective To assess the influence of time of sampling on the value of CSF tests in the diagnosis of sCJD. Method In the framework of a multinational European study, we studied the results of 14-3-3, S100b, neurone specific enolase (NSE) and tau protein in 833 CSF samples from sCJD patients at different stages of disease and in 66 sequentially repeated lumbar punctures (LP). Results 14-3-3 and tau protein tended to increase in sensitivity from onset (88%, 81%) to the advanced stage (91%, 90%). This was significant only in the methionine-valine (MV) heterozygous group of patients at codon 129. The absolute levels of S100b (p < 0.05), NSE and tau protein increased in the last stage of disease. High levels of tau protein, NSE and S100b were associated with shorter survival times (p < 0.01). Sixty-six sCJD patients underwent repeated LP. These sCJD patients were younger, had longer disease durations and were more frequently MV at codon 129 (p < 0.001) than the whole group. 14-3-3 sensitivity increased from 64% to 82% in the second LP (p = 0.025) and 88% sCJD patients had at least one positive result. Conclusions Sensitivity and absolute levels of CJD markers increased with disease progression and were modulated by the codon 129 genotype. Early negative results should be inter-preted with caution, especially in young patients or those who are MV at codon 129.

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“…Extensive destruction of the brain leads to leakage of 14-3-3 proteins into the cerebrospinal fluid (CSF), which can be detected by ELISA (Kenney et al, 2000;Green et al, 2002) or Western blotting (Hsich et al, 1996;Takahashi et al, 1999). Elevated 14-3-3 levels are found in the CSF of patients with dementia (Burkhard et al, 2001) or suffering from prion diseases (Hsich et al, 1996;Collins et al, 2000;Zerr et al, 2000;Giraud et al, 2002;Geschwind et al, 2003). In this regard, detection of 14-3-3 proteins in CSF is not disease-specific, but rather reflects the process of damaged neurons spilling their proteins into CSF (Pocchiari et al, 2004;Cuadrado-Corrales et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Time-course studies of 14-3-3 protein isoforms in cerebrospinal fluid and brain of primates after oral or intracerebral infection with bovine spongiform encephalopathy agent

Yutzy

Holznagel

Coulibaly

et al. 2007

Journal of General Virology

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Experimental transmission of bovine spongiform encephalopathy (BSE) to cynomolgus monkeys (Macaca fascicularis) is an animal model for variant Creutzfeldt–Jakob disease (vCJD). The presence of 14-3-3 proteins in cerebrospinal fluid (CSF) samples indicates neuronal destruction and is therefore used as a clinical biomarker. However, time-course studies using 14-3-3 proteins have not been performed until now in simian vCJD. The main goals of this study were to determine isoform patterns, to examine kinetics and to correlate the clinical course with the occurrence of this biomarker in simian vCJD. In monkeys dosed intracerebrally with BSE, the earliest clinical sign of illness was a drop in body weight that was detected months before the onset of mild neurological signs. Macaques dosed orally or intracerebrally with BSE developed neurological signs 4.3 (3.7–4.6) and 4.8 (2.9–6.0) years post-infection, respectively. 14-3-3β- and -γ-positive CSF samples were found around the time of onset of mild neurological signs, but not earlier. In contrast, 14-3-3ϵ and -η isoforms were not detectable. 14-3-3 levels increased with time and were positively correlated with the degree of neurological symptoms. Post-mortem examination of brain samples revealed a positive correlation between PrPres and 14-3-3ϵ levels. Interestingly, florid plaques characteristic of human vCJD could not be detected in diseased monkeys. It was concluded that analysis of 14-3-3 proteins in CSF is a reliable tool to characterize the time course of brain degeneration in simian vCJD. However, there are differences in the clinical course between orally and intracerebrally infected animals that may influence the detection of other biomarkers.

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Increased Detection of 14-3-3 Protein in Cerebrospinal Fluid in Sporadic Creutzfeldt-Jakob Disease during the Disease Course

Cited by 20 publications

References 10 publications

CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease

CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease

Influence of timing on CSF tests value for Creutzfeldt-Jakob disease diagnosis

Time-course studies of 14-3-3 protein isoforms in cerebrospinal fluid and brain of primates after oral or intracerebral infection with bovine spongiform encephalopathy agent

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