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

Artikel i vetenskaplig tidskrift
Författare Brit Mollenhauer
Frederick DuBois Bowman
Daniel Drake
Jimmy Duong
Kaj Blennow
Omar El-Agnaf
Leslie M Shaw
Jennifer Masucci
Peggy Taylor
Robert M Umek
Jill M Dunty
Chris L Smith
Erik Stoops
Hugo Vanderstichele
Adrian W Schmid
Marc Moniatte
Jing Zhang
Niels Kruse
Hilal A Lashuel
Charlotte Teunissen
Tanja Schubert
Kuldip D Dave
Samantha J Hutten
Henrik Zetterberg
Publicerad i Journal of neurochemistry
Volym 149
Nummer/häfte 1
Sidor 126-138
ISSN 1471-4159
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 126-138
Språk en
Länkar dx.doi.org/10.1111/jnc.14569
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Neurokemi

Sammanfattning

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.

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