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Antibody‐based methods for the measurement of α‐synuclein concentration in human cerebrospinal fluid – method comparison and round robin study
Author(s) -
Mollenhauer Brit,
Bowman Frederick DuBois,
Drake Daniel,
Duong Jimmy,
Blennow Kaj,
ElAgnaf Omar,
Shaw Leslie M.,
Masucci Jennifer,
Taylor Peggy,
Umek Robert M.,
Dunty Jill M.,
Smith Chris L.,
Stoops Erik,
Vanderstichele Hugo,
Schmid Adrian W.,
Moniatte Marc,
Zhang Jing,
Kruse Niels,
Lashuel Hilal A.,
Teunissen Charlotte,
Schubert Tanja,
Dave Kuldip D.,
Hutten Samantha J.,
Zetterberg Henrik
Publication year - 2019
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14569
Subject(s) - cerebrospinal fluid , biomarker , dementia with lewy bodies , lewy body , parkinson's disease , reproducibility , pathology , chemistry , medicine , dementia , chromatography , disease , biochemistry
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 ( R 2 0.83–0.99), and good correlation with each other ( R 2 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.