Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study
Open accessAbstract
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.
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Consensus on a cerebrospinal fluid profile of reduced αSyn in synucleinopathy patients is still lacking mainly due to high variability between αSyn quantification assays, differences in the species of αSyn being quantified and inter-laboratory variability.
“consensus on a CSF profile of reduced αSyn in synucleinopathy patients is still lacking mainly due to the high variability between the various αSyn quantification assays, differences in the species of αSyn being quantified and inter-laboratory variability [96].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [96]
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α-synuclein in the pathophysiology of Alzheimer’s disease
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- Authors
- 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., Kuiperij, H. B., Leitão, M. J., Lleó, A., Martins, M., Matos, M., Mollergard, H. M., Nobili, F., Öhrfelt, A., Parnetti, L., de Oliveira, C. R., Rot, U., Sáez-Valero, J., Struyfs, H., Tanassi, J. T., Taylor, P., Tsolaki, M., Vanmechelen, E., Verbeek, M. M., Zilka, N., Blennow, K., Zetterberg, H., & Mollenhauer, B.
- Affiliations
- Universitätsmedizin Göttingen (DE)
- Sahlgrenska University Hospital (SE)
- Hospital de Sant Pau (ES)
- Statens Serum Institut (DK)
- University of Genoa (IT)
- University of Perugia (IT)
- University of Antwerp (BE)
- Dokuz Eylül University (TR)
- Akershus University Hospital (NO)
- University of Geneva (CH)
- Aristotle University of Thessaloniki (GR)
- Instituto de Medicina Molecular João Lobo Antunes (PT)
- Slovak Academy of Sciences (SK)
- Radboud University Nijmegen (NL)
- Unidade Local de Saúde de Coimbra (PT)
- BioLegend (United States) (US)
- ADx NeuroSciences (BE)
- Corresponding author
- Kruse, Niels
- ORCID
- Kruse, Niels
- Alcolea, Daniel
- Capello, Elisabetta
- Chiasserini, Davide
- Engelborghs, Sebastiaan
- Eren, Erden
- Fladby, Tormod
- Frisoni, Giovanni
- Gkatzima, Olymbia
- Kováčech, Branislav
- Kuiperij, H. Bea
- Leitão, Maria J.
- Lleó, Alberto
- Martins, Madalena
- Matos, Mafalda
- Nobili, Flavio
- Öhrfelt, Annika
- Parnetti, Lucilla
- de Oliveira, Catarina Resende
- Tanassi, Julia T.
- Tsolaki, Magda
- Vanmechelen, Eugeen
- Verbeek, Marcel M.
- Blennow, Kaj
- Zetterberg, Henrik
- Mollenhauer, Brit
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 36
- Issue
- 9
- Pages
- 2587-2596
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1827206004
- Cited by
- 38
- References
- 27
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2022: 2 · 2021: 1 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 3
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- GRO (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- The Alzheimer Research Foundation ((grant number S#12018)
- Danish Council for Strategic Research (grant number 0603-00511B)
- Bundesministerium für Bildung und Forschung (grant number OIED1203C)
- General Secretary of Research and Technology
- Ministry of Health
- Fundação para a Ciência e a Tecnologia (grant numbers JPND/0004/2011, IMM/BPD/51-2013, IMM/BI/7-2013, JPND/0005/2011)
- Fondo de
- Instituto de Salud Carlos III (grant numbers PI11/03026, PI11/03035)
- The Slovenian Research Agency, Slovenia (grant number A3-0001); The Swedish Research Council
- Netherlands Organisation for Health Research and Development (grant number 629000002)
- Scientific and Technological Research Council of Turkey (grant number 112S335)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- alpha-synuclein, cerebrospinal fluid, Parkinson's disease, synucleinopathies, ELISA validation, assay standardization, pre-analytical variability, lot-to-lot variation, biomarkers
- MeSH terms
- Enzyme-Linked Immunosorbent Assay, Europe, Female, Humans, International Cooperation, Male, Parkinson Disease, United States, Reproducibility of Results, Biomarkers, Neurodegenerative Diseases, alpha-Synuclein
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