Journal
JOURNAL OF NEUROLOGY
Volume 262, Issue 10, Pages 2305-2311Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00415-015-7837-x
Keywords
Cerebrospinal fluid; Biomarkers; Neurodegeneration; Alzheimer's disease; Creutzfeldt-Jakob disease; Electrochemiluminescence-based detection system; ELISA
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Funding
- 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]
- Alzheimer-Forschungs-Initiative e.V. [AFI 12851]
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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, beta-amyloid 1-42 (A beta 42) and alpha-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, alpha-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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