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J Neurochem. 2019 Apr;149(1):126-138. doi: 10.1111/jnc.14569. Epub 2018 Nov 13.

Antibody-based methods for the measurement of α-synuclein concentration in human cerebrospinal fluid - method comparison and round robin study.

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Paracelsus-Elena-Klinik, Kassel, Germany.
Department of Neurology, University Medical Center, Goettingen, Germany.
Department of Biostatistics, Columbia University, Mailman School of Public Health, New York City, New York, USA.
Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), and College of Science and Engineering, HBKU, Education City, Qatar Foundation, Doha, Qatar.
Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA.
BioLegend, Dedham, MA, USA.
Meso Scale Discovery, Gaithersburg, MD, USA.
ADx NeuroSciences, Gent, Belgium.
Proteomics Core Facility, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
University of Washington, Seattle, WA, USA.
Institute of Neuropathology, University Medical Center, Goettingen, Germany.
Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Institute of Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015, Lausanne, Switzerland.
VU University Medical Center, Amsterdam, the Netherlands.
Bioclinica, Lyon, France.
Michael J. Fox Foundation for Parkinson's Research, New York City, New York, USA.
Department of Molecular Neuroscience, UCL Institute of Neurology, Queens Square, London, UK.
UK Dementia Research Institute at UCL, London, UK.


α-Synuclein is the major component of Lewy bodies and a candidate biomarker for neurodegenerative diseases in which Lewy bodies are common, including Parkinson's disease and dementia with Lewy bodies. A large body of literature suggests that these disorders are characterized by reduced concentrations of α-synuclein in cerebrospinal fluid (CSF), with overlapping concentrations compared to healthy controls and variability across studies. Several reasons can account for this variability, including technical ones, such as inter-assay and inter-laboratory variation (reproducibility). We compared four immunochemical methods for the quantification of α-synuclein concentration in 50 unique CSF samples. All methods were designed to capture most of the existing α-synuclein forms in CSF ('total' α-synuclein). Each of the four methods showed high analytical precision, excellent correlation between laboratories (R2 0.83-0.99), and good correlation with each other (R2 0.64-0.93), although the slopes of the regression lines were different between the four immunoassays. The use of common reference CSF samples decreased the differences in α-synuclein concentration between detection methods and technologies. Pilot data on an immunoprecipitation mass spectrometry (IP-MS) method is also presented. Our results suggest that the four immunochemical methods and the IP-MS method measure similar forms of α-synuclein and that a common reference material would allow harmonization of results between immunoassays.


biomarker; cerebrospinal fluid; enzyme-linked immunoabsorbent assay; mass spectrometry; round robin; α-synuclein

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