Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study

Niels Kruse, Staffan Persson, Daniel Alcolea, Justyna M C Bahl, Ines Baldeiras, Elisabetta Capello, Davide Chiasserini, Luisella Bocchio Chiavetto, Andreja Emersic, Sebastiaan Engelborghs, Erden Eren, Tormod Fladby, Giovanni Frisoni, María Salud García-Ayllón, Sermin Genc, Olymbia Gkatzima, Niels H H Heegaard, André M. Janeiro, Branislav Kováčech, H. Bea KuiperijMaria J. Leitão, Alberto Lleó, Madalena Martins, Mafalda Matos, Hanne M. Mollergard, Flavio Nobili, Annika Öhrfelt, Lucilla Parnetti, Catarina Resende de Oliveira, Uros Rot, Javier Sáez-Valero, Hanne Struyfs, Julia T. Tanassi, Peggy Taylor, Magda Tsolaki, Eugeen Vanmechelen, Marcel M. Verbeek, Norbert Zilka, Kaj Blennow, Henrik Zetterberg, Brit Mollenhauer

Research output: Contribution to journalArticle

Abstract

Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program - Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis. Our study showed that although factors such as preanalytical sample handling and lot-to-lot variability were minimized by our study design, we identified high variation in absolute values of CSF aSyn even when the same samples and same lots of assays were applied. We further demonstrate that although absolute concentrations differ between laboratories the quantitative results are comparable. With further standardization this assay may become an attractive tool for comparing aSyn measurements in diverse settings. Recommendations for further validation experiments and improvement of the interlaboratory results obtained are given.

Original languageEnglish
Pages (from-to)2587-2596
Number of pages10
JournalNeurobiology of Aging
Volume36
Issue number9
DOIs
Publication statusPublished - Sep 1 2015

Keywords

  • Alpha-synuclein
  • Biomarker
  • Cerebrospinal fluid
  • ELISA
  • Validation

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

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  • Cite this

    Kruse, N., Persson, S., Alcolea, D., Bahl, J. M. C., Baldeiras, I., Capello, E., Chiasserini, D., Bocchio Chiavetto, L., Emersic, A., Engelborghs, S., Eren, E., Fladby, T., Frisoni, G., García-Ayllón, M. S., Genc, S., Gkatzima, O., Heegaard, N. H. H., Janeiro, A. M., Kováčech, B., ... Mollenhauer, B. (2015). Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study. Neurobiology of Aging, 36(9), 2587-2596. https://doi.org/10.1016/j.neurobiolaging.2015.05.003