Plasma and CSF neurofilament light chain measured by Simoa and Lumipulse: an inter-platform comparison across neurological disorders
Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction Blood neurofilament light chain (NfL) is an accessible biomarker of neuroaxonal injury across a broad range of neurological disorders, but its clinical implementation requires robust cross-platform analytical and clinical comparability. The objective of this study was to evaluate the analytical and clinical comparability of plasma NfL measurements using Simoa and Lumipulse across different neurological conditions, by assessing cross-platform agreement and the ability of both assays to distinguish neurological diseases from healthy controls. Paired CSF analyses were performed in a subset of participants to biologically anchor plasma findings to the central compartment. Methods 383 individuals were included, comprising healthy controls and patients with neurodegenerative conditions, multiple sclerosis and stroke. Plasma NfL was measured in all participants using both Simoa and Lumipulse, with paired CSF analyses in a subset of 92 individuals. The Lumipulse testing intermediate precision and between-day repeatability was assessed as by the CLSI EP15. Cross-platform agreement for plasma NfL was evaluated using correlation analyses, Passing–Bablok regression and Bland–Altman analysis. Associations between plasma/CSF NfL concentrations were assessed using Spearman’s rank correlation analysis for each platform, separately. Age-adjusted cross-diagnostic differences were evaluated using permutation ANCOVA and multiple linear regression models for each platform, separately. Results Plasma NfL measured by Simoa and Lumipulse showed strong cross-platform concordance in the whole cohort (ρ=0.90), with similarly strong concordance observed for CSF NfL in the subset with paired samples (ρ=0.90). Method-comparison analyses in plasma demonstrated consistent agreement between platforms, with identifiable constant and proportional bias, alongside systematically higher absolute plasma NfL values measured by Lumipulse. Within-platform analyses showed significant correlations between plasma and CSF NfL concentrations (ρ=0.72 for Simoa; ρ=0.78 for Lumipulse). Noteworthy, Lumipulse NfL CSF and Blood kits exhibited high precision and analytical accuracy. Across both assays, plasma NfL increased with age and was significantly elevated in patients with neurological disorders compared with healthy controls. Discussion Simoa and Lumipulse capture a consistent biological signal in plasma across patients with neurological disorders, although their absolute NfL values differ, supporting the use of platform-specific reference ranges in clinical practice.
Authors: Andrea Toja, Virginia Quaresima, Chiara Tolassi, Tommaso Merati, Chiara Trasciatti, Simona G. Signorini, Andrea Morotti, Francesco Berinato, Loris Poli, Liberato Stabile, Irene Girotto, Marianna Bertoni, Cinzia Zatti, Alessandro Magliozzi, Caterina Martinuzzo, Claudia Pangrazio, Klaudia Eshja, Giulia Foresti, Ilenia Libri, Eqrem Rusi, Marta Bianchi, Viviana Cristillo, Irene Volonghi, Alice Galli, Andrea Rizzardi, Salvatore Caratozzolo, Chiara Agosti, Rosanna Colao, Carmelo Rodolico, Elena Marcello, Fabrizio Gardoni, Monica Di Luca, Henrik Zetterberg, Nicholas J. Ashton, Duilio Brugnoni, Andrea Pilotto, Alessandro Padovani
Institutions: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Brescia, Presidio Ospedaliero Lamezia Terme, University of Messina, University of Milan, Sahlgrenska University Hospital, University of Gothenburg, University of Arizona, Banner Sun Health Research Institute, Banner Alzheimer’s Institute
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: European Commission
OpenAlex ID: W7163385605