14-3-3 CSF levels in sporadic Creutzfeldt–Jakob disease differ across molecular subtypes

Gmitterová, Karin; Heinemann, Uta; Bodemer, Monika; Krasnianski, Anna; Meissner, Bettina; Kretzschmar, H. A.; Zerr, Inga

doi:10.1016/j.neurobiolaging.2008.01.007

Cited by 57 publications

(59 citation statements)

References 39 publications

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“…As tau is a marker of neurodegeneration, it seems reasonable to consider the speed of neuronal loss as a molecular equivalent of disease progression rates; however, other neuropathological processes like astrogliosis, PrP deposition or plaque formation might also play a role. Subtypespecific findings attributable to different rates of disease progression have been described in a similar way for proteins 14-3-3 and MRI profiles (Gmitterova, et al, 2009); however, these findings have not been transferred to clinical practice, because 14-3-3 ELISA results are not commonly available and MRI profile differentiation needs expert radiological rating. Total tau, on the other hand, is a widely available test which can also be applied in resource-poor settings.…”

Section: Discussionmentioning

confidence: 89%

“…Cerebrospinal fluid (CSF) levels of one classic marker of neurodegeneration, protein 14-3-3, have been shown to differ between molecular subtypes when using a 14-3-3 ELISA (Gmitterova, et al, 2009). However, as 14-3-3 is routinely assessed in a binary way by Western Blot (resulting in high positivity rates for all subtypes and no detection of quantitative differences), 14-3-3 has not been adopted in clinical practice in order to differentiate between subtypes during life-time.…”

Section: Introductionmentioning

confidence: 99%

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

Karch¹,

Hermann²,

Ponto³

et al. 2015

Neurobiology of Aging

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CitationCerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease. 2015, 36 Abstract:The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during life-time. Since the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows pre-mortem diagnosis of molecular subtype when codon 129 genotype is known.296 sCJD patients were tested for their cerebrospinal fluid total tau level at time of diagnosis and were investigated for their sCJD subtype post-mortem.There was a significant association between tau levels and the prion protein type in patients with Highlights: To date, subtype determination in Creutzfeldt-Jakob disease is only possible post-mortem  We investigate if total tau can be used as a subtype-specific marker for Creutzfeldt-Jakob disease  In our study we show that total tau has a good diagnostic validity when codon 129 genotype is known  Thus, we propose the combination of total tau and codon 129 genotype as a new test for molecular subtype  This approach provides valuable information for caretakers about the further course of disease

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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

Karch¹,

Hermann²,

Ponto³

et al. 2015

Neurobiology of Aging

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“…It has been suggested that many factors impact prion disease biomarker appearance including disease strain, subtype, duration, age at onset, and timing of lumbar puncture [7,32–40]. For example, when 70 sCJD cases with distinct molecular subtypes were evaluated for 14-3-3 using ELISA, the most elevated levels of 14-3-3 were observed in classical molecular subtypes (MM1), and lower levels were observed with less common subtypes (MV2, MM2) with longer durations and atypical presentations of CJD [41]. CSF biomarkers in sCJD have been tracked over the clinical course of disease [42,43] but have not been examined during the preclinical asymptomatic phase of the disease.…”

Section: Introductionmentioning

confidence: 99%

14-3-3 and enolase abundances in the CSF of Prion diseased rats

Gushue

Herbst

Sim

et al. 2018

Prion

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Creutzfeldt-Jakob disease (CJD) is characterized by an extended asymptomatic preclinical phase followed by rapid neurodegeneration. There are no effective treatments. CJD diagnosis is initially suspected based upon the clinical presentation of the disease and the exclusion of other etiologies. Neurologic symptoms are assessed in combination with results from cerebrospinal fluid (CSF) biomarker abundances, electroencephalography (EEG), magnetic resonance imaging (MRI), and in some countries, real-time quaking-induced conversion (RT-QuIC). Inconsistencies in sensitivities and specificities of prion disease biomarker abundance in CSF have been described, which can affect diagnostic certainty, but the utility of biomarkers for prognosis has not been fully explored. The clinical presentation of CJD is variable, and factors such as prion protein polymorphic variants, prion strain, and other genetic or environmental contributions may affect the disease progression, confounding the appearance or abundance of biomarkers in the CSF. These same factors may also affect the appearance or abundance of biomarkers, further confounding diagnosis. In this study, we controlled for many of these variables through the analysis of serial samples of CSF from prion-infected and control rats. Prion disease in laboratory rodents follows a defined disease course as the infection route and time, prion strain, genotype, and environmental conditions are all controlled. We measured the relative abundance of 14-3-3 and neuron-specific enolase (NSE) in CSF during the course of prion infection in rats. Even when disease-related, environmental and genetic variables were controlled, CSF 14-3-3 and NSE abundances were variable. Our study emphasizes the considerable diagnostic and prognostic limitations of these prion biomarkers.

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“…Most widely used surrogate protein markers are brain derived CSF proteins (14-3-3, t-PrP, total (t)-tau and t-tau/phosphorylated (p)-tau ratio) with different level of specificity and sensitivity for differential diagnosis of CJD from other rapidly progressive dementias [8,18,20,[39][40][41][42][43]. While many studies have analysed utility of these biomarkers for differential diagnosis, only few studies have particularly analysed the effect of the disease-subtypes on the specificity and sensitivity of the biomarkers [23,24,44]. Recently, we showed that CSF protein analysis (14-3-3, tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid β1-42, S100B and NSE can be used as a marker for pre-mortem diagnosis of sCJD subtypes when genotype of codon 129 is known [44,45].…”

Section: Introductionmentioning

confidence: 99%

“…While many studies have analysed utility of these biomarkers for differential diagnosis, only few studies have particularly analysed the effect of the disease-subtypes on the specificity and sensitivity of the biomarkers [23,24,44]. Recently, we showed that CSF protein analysis (14-3-3, tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid β1-42, S100B and NSE can be used as a marker for pre-mortem diagnosis of sCJD subtypes when genotype of codon 129 is known [44,45]. Authors have reported significantly high tau levels in PrP type 1 patient with MM and MV genotype but lower in VV cases.…”

Section: Introductionmentioning

confidence: 99%