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Quantification of CSF biomarkers using an electrochemiluminescence-based detection system in the differential diagnosis of AD and sCJD

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Abstract

The identification of reliable diagnostic tools for the differential diagnosis between sporadic Creutzfeldt–Jakob Disease (sCJD) and Alzheimer’s disease (AD) remains impeded by the existing clinical, neuropathological and molecular overlap between both diseases. The development of new tools for the quantitative measurement of biomarkers is gaining experimental momentum due to recent advances in high-throughput screening analysis and with the optimization of assays for their quantification in biological fluids, including cerebrospinal fluid (CSF). Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve clinical quality performance in a variety of sample types due to its high sensitivity and dynamic range. Here, we quantified the CSF levels of Tau-protein, β-amyloid 1-42 (Aβ42) and α-synuclein, as important biomarkers in CSF used in the differential diagnosis of neurodegenerative disorders in 12 AD, 12 sCJD and 12 control cases by singleplex ECL-based technology. Its performance has been compared to classical enzyme-linked immunosorbent assays (ELISA) to confront their clinical accuracy. ECL-based technology validates previous data obtained with ELISA and presents a higher performance in the discrimination of three analysed groups as determined by increased area under the curve (AUC) values for the three biomarkers. Importantly, α-synuclein levels detected by ECL allow an excellent discrimination between sCJD cases and AD and control cases, unveiling a new clinical approach for the differential diagnosis of sCJD.

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Acknowledgments

The authors would like to thank Barbara Ciesielczyk and Siri Reuter for excellent technical assistance. The work was supported by: PRIORITY PROJECT (EU): Protecting the food chain from prions: shaping European priorities through basic and applied research (FP7-KBBE-2007-2A), JPND––DEMTEST (EU): Biomarker-based diagnosis of rapidly progressive dementias––optimization of diagnostic protocols (01ED1201A) and Alzheimer-Forschungs-Initiative e.V. (AFI 12851).

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Authors and Affiliations

  1. Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University and German Center for Neurodegenerative Diseases (DZNE), Robert-Koch-Str. 40, 37075, Goettingen, Germany

    Franc Llorens, Matthias Schmitz, Mohsin Shafiq, Nadine Gotzman, Saima Zafar, Katrin Thune & Inga Zerr

  2. Institute for Neuropathology, University Medical Center Göttingen, Göttingen, Germany

    Niels Kruse & Brit Mollenhauer

  3. Keizo Asami Laboratory, Federal University of Pernambuco, Recife, Brazil

    José Eriton Gomes da Cunha & João Ricardo Mendes de Oliveira

  4. Paracelsus-Elena Klinik, Center for Parkinsonism and Movement Disorders, Kassel, Germany

    Brit Mollenhauer

  5. Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany

    Brit Mollenhauer

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  1. Franc Llorens
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  2. Niels Kruse
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Correspondence to Franc Llorens.

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Ethical standard

The study has been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. As stated in the text, all persons gave their informed consent prior to their inclusion in the study and samples were anonymised.

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415_2015_7837_MOESM1_ESM.pptx

Supplementary material 1 (PPTX 54 kb). Correlations between S100B and α-synuclein levels in sCJD cases. Graph showing the correlation between S100B and α-synuclein levels in the CSF of sCJD cases. R value is indicated. S100B cut-off value for sCJD diagnostic is shown. One sCJD case is under the S100 cut-off value 4.2 ng/ml). The same case presents the lowest α-synuclein level among the sCJD cohort

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Llorens, F., Kruse, N., Schmitz, M. et al. Quantification of CSF biomarkers using an electrochemiluminescence-based detection system in the differential diagnosis of AD and sCJD. J Neurol 262, 2305–2311 (2015). https://doi.org/10.1007/s00415-015-7837-x

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  • DOI: https://doi.org/10.1007/s00415-015-7837-x

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