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Neuroscience. 2016 May 13;322:398-407. doi: 10.1016/j.neuroscience.2016.02.057. Epub 2016 Mar 3.

Sporadic Creutzfeldt-Jakob disease diagnostic accuracy is improved by a new CSF ELISA 14-3-3γ assay.

Author information

1
Neurochemistry Laboratory, Neurology Department, University Hospital Coimbra, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Portugal; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, Faculty of Medicine, Pólo I, 1st Floor, 3004-504 Coimbra, Portugal. Electronic address: jajao86@gmail.com.
2
Neurochemistry Laboratory, Neurology Department, University Hospital Coimbra, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Portugal; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, Faculty of Medicine, Pólo I, 1st Floor, 3004-504 Coimbra, Portugal.
3
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, Faculty of Medicine, Pólo I, 1st Floor, 3004-504 Coimbra, Portugal.
4
Neurochemistry Laboratory, Neurology Department, University Hospital Coimbra, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Portugal.
5
Neurology Department, University Hospital Coimbra, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, Portugal.
6
Neurology Department, St Marcos Hospital, Braga, Portugal.
7
Neurology Department, University Hospital Coimbra, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Portugal; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, Faculty of Medicine, Pólo I, 1st Floor, 3004-504 Coimbra, Portugal.
8
Neurochemistry Laboratory, Neurology Department, University Hospital Coimbra, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, Portugal; Neurology Department, University Hospital Coimbra, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Portugal; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, Faculty of Medicine, Pólo I, 1st Floor, 3004-504 Coimbra, Portugal.

Abstract

Protein 14-3-3 is a reliable marker of rapid neuronal damage, specifically increased in cerebrospinal fluid (CSF) of sporadic Creutzfeldt-Jakob disease (sCJD) patients. Its detection is usually performed by Western Blot (WB), prone to methodological issues. Our aim was to evaluate the diagnostic performance of a recently developed quantitative enzyme-linked immunosorbent (ELISA) assay for 14-3-3γ, in comparison with WB and other neurodegeneration markers. CSF samples from 145 patients with suspicion of prion disease, later classified as definite sCJD (n=72) or Non-prion diseases (Non-CJD; n=73) comprised our population. 14-3-3 protein was determined by WB and ELISA. Total Tau (t-Tau) and phosphorylated Tau (p-Tau) were also evaluated. Apolipoprotein E gene (ApoE) and prionic protein gene (PRNP) genotyping was assessed. ELISA 14-3-3γ levels were significantly increased in sCJD compared to Non-CJD patients (p<0.001), showing very good accuracy (AUC=0.982; sensitivity=97%; specificity=94%), and matching WB results in 81% of all cases. It strongly correlated with t-Tau and p-Tau (p<0.0001), showing slightly higher specificity (14-3-3 WB - 63%; Tau - 90%; p-Tau/t-Tau ratio - 88%). From WB inconclusive results (n=44), ELISA 14-3-3γ correctly classified 41 patients. Additionally, logistic regression analysis selected ELISA 14-3-3γ as the best single predictive marker for sCJD (overall accuracy=93%). ApoE and PRNP genotypes did not influence ELISA 14-3-3γ levels. Despite specificity for 14-3-3γ isoform, ELISA results not only match WB evaluation but also help discrimination of inconclusive results. Our results therefore reinforce this assay as a single screening test, allowing higher sample throughput and unequivocal results.

KEYWORDS:

14-3-3 protein; CSF; ELISA; Tau proteins; Western Blot; sCJD

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