The 14-3-3 Brain Protein in Cerebrospinal Fluid as a Marker for Transmissible Spongiform Encephalopathies

Hsich, Gary; Kenney, Kimbra; Gibbs, Clarence J.; Lee, Kelvin H.; Harrington, Michael G.

doi:10.1056/nejm199609263351303

Cited by 607 publications

(414 citation statements)

References 31 publications

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“…Protein 14-3-3 was analysed in all study participants by Western blot according to previously published protocols [6,16]. Western blot results were classified in a binary way (negative= no band present, positive= band present).…”

Section: Csf Analysesmentioning

confidence: 99%

Diagnostic profiles of patients with late-onset Creutzfeldt–Jakob disease differ from those of younger Creutzfeldt–Jakob patients: a historical cohort study using data from the German National Reference Center

et al. 2014

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Section: Csf Analysesmentioning

confidence: 99%

Diagnostic profiles of patients with late-onset Creutzfeldt–Jakob disease differ from those of younger Creutzfeldt–Jakob patients: a historical cohort study using data from the German National Reference Center

et al. 2014

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“…The detection of 14-3-3 proteins and measurement of phosphorylated tau protein in the cerebrospinal fluid has been found to be useful in supporting the clinical diagnosis of CJD (3,4). Although these tests are clinically useful, they are surrogate markers and therefore cannot provide direct evidence of the presence of PrP Sc .…”

mentioning

confidence: 99%

A Pitfall in Diagnosis of Human Prion Diseases Using Detection of Protease-resistant Prion Protein in Urine

Furukawa

Doh‐ura

Okuwaki

et al. 2004

Journal of Biological Chemistry

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Because a definite diagnosis of prion diseases relies on the detection of the abnormal isoform of prion protein (PrP Sc ), it has been urgently necessary to establish a non-invasive diagnostic test to detect PrP Sc in human prion diseases. To evaluate diagnostic usefulness and reliability of the detection of protease-resistant prion protein in urine, we extensively analyzed proteinase K (PK)-resistant proteins in patients affected with prion diseases and control subjects by Western blot, a coupled liquid chromatography and mass spectrometry analysis, and N-terminal sequence analysis. The PK-resistant signal migrating around 32 kDa previously reported by Chem. 276, 31479 -31482) was not observed in this study. Instead, discrete protein bands with an apparent molecular mass of ϳ37 kDa were detected in the urine of many patients affected with prion diseases and two diseased controls. Although these proteins also gave strong signals in the Western blot using a variety of anti-PrP antibodies as a primary antibody, we found that the signals were still detectable by incubation of secondary antibodies alone, i.e. in the absence of the primary antiPrP antibodies. Mass spectrometry and N-terminal protein sequencing analysis revealed that the majority of the PK-resistant 37-kDa proteins in the urine of patients were outer membrane proteins (OMPs) of the Enterobacterial species. OMPs isolated from these bacteria were resistant to PK and the PK-resistant OMPs from the Enterobacterial species migrated around 37 kDa on SDS-PAGE. Furthermore, nonspecific binding of OMPs to antibodies could be mistaken for PrP Sc . These findings caution that bacterial contamination can affect the immunological detection of prion protein. Therefore, the presence of Enterobacterial species should be excluded in the immunological tests for PrP Sc in clinical samples, in particular, urine.

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“…The 14-3-3 protein in the CSF has been reported to have a sensitivity between 85% and 96% and a specificity between 79% and 96%. As it may be present in other conditions such as viral encephalitis, metabolic encephalopathy and cerebral hemorrhages, the test is not appropriate as a general screening test for CJD, but is useful for diagnosis of truly suspect cases (14)(15)(16). In contrast to qualitative 14-3-3 test, ELISA immunoassay for the quantitative detection of tau protein in CSF has shown superior accuracy with less ambiguous results (17).…”

Section: Discussionmentioning

confidence: 99%

Positive 14-3-3 and tau proteins in a sporadic Creutzfeldt-Jakob disease case and a brief perspective of prion diseases in Colombia

Escandón-Vargas¹,

Zorrilla-Vaca²,

Corral-Prado³

2016

biomedica

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Prion diseases are rare neurodegenerative disorders occurring worldwide and affecting both humans and animals. Herein, we present the case of a patient diagnosed with definite sporadic CreutzfeldtJakob disease in Cali, Colombia. Besides neurological examination, 14-3-3 and tau proteins were valuable tools supporting the diagnosis. We also present a brief perspective of the prion diseases reported in Colombia to date. Although the incidence of prion diseases is unknown in Colombia, our literature review revealed that one case of scrapie in 1981 and 29 human sporadic cases of Creutzfeldt-Jakob disease have been documented and published in our country.Key words: Creutzfeldt-Jakob syndrome, prions, case reports. doi: http://dx.doi.org/10.7705/biomedica.v36i3.2729 Proteínas 14-3-3 y tau positivas en un caso de enfermedad esporádica de Creutzfeldt-Jakob y una breve reseña de las enfermedades priónicas en Colombia Las enfermedades priónicas son alteraciones neurodegenerativas raras que ocurren en todo el mundo y afectan tanto a humanos como a animales. En el presente artículo, se reporta un caso con diagnóstico confirmado de enfermedad esporádica de Creutzfeldt-Jakob. Además del examen neuropatológico, las proteínas 14-3-3 y tau fueron herramientas valiosas que ayudaron en el diagnóstico. También, se presenta una breve reseña de las enfermedades priónicas reportadas en Colombia hasta la fecha. Aunque en el país se desconoce la incidencia de las enfermedades priónicas, nuestra búsqueda en la literatura científica reveló informes publicados sobre un caso de tembladera de las ovejas (scrapie o encefalopatía espongiforme ovina) en 1981 y 29 casos esporádicos de Creutzfeldt-Jakob en el país.Palabras clave: síndrome de Creutzfeldt-Jakob, priones, informes de casos.

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The 14-3-3 Brain Protein in Cerebrospinal Fluid as a Marker for Transmissible Spongiform Encephalopathies

Abstract: In patients with dementia, a positive immunoassay for the 14-3-3 brain protein in cerebrospinal fluid strongly supports a diagnosis of Creutzfeldt-Jakob disease. This finding, however, does not support the use of the test in patients without clinically evident dementia.

Cited by 607 publications

References 31 publications

Diagnostic profiles of patients with late-onset Creutzfeldt–Jakob disease differ from those of younger Creutzfeldt–Jakob patients: a historical cohort study using data from the German National Reference Center

Diagnostic profiles of patients with late-onset Creutzfeldt–Jakob disease differ from those of younger Creutzfeldt–Jakob patients: a historical cohort study using data from the German National Reference Center

A Pitfall in Diagnosis of Human Prion Diseases Using Detection of Protease-resistant Prion Protein in Urine

Positive 14-3-3 and tau proteins in a sporadic Creutzfeldt-Jakob disease case and a brief perspective of prion diseases in Colombia

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