Plasma and CSF neurofilament light chain measured by Simoa and Lumipulse: an inter-platform comparison across neurological disorders

Blood neurofilament light chain (NfL) is an accessible biomarker of neuroaxonal injury, but clinical implementation requires robust analytical comparability across platforms. We evaluated plasma NfL measured by Simoa and Lumipulse across neurological disorders, including paired CSF analyses to anchor plasma findings to the central compartment.

We included 383 individuals, comprising healthy controls and patients with neurodegenerative diseases, multiple sclerosis, and ischemic stroke. Plasma NfL was measured in all participants using Simoa and Lumipulse; paired CSF measurements were available in 92 individuals. Lumipulse intermediate precision and between-day repeatability were assessed according to CLSI EP15. Cross-platform agreement was evaluated using Spearman correlation, Passing-Bablok regression, and Bland-Altman analysis. Plasma-CSF associations and age-adjusted diagnostic differences were assessed separately for each platform.

Plasma NfL measured by Simoa and Lumipulse showed strong concordance in the whole cohort (ρ=0.90), with similarly strong CSF concordance in paired samples (ρ=0.90). Method-comparison analyses demonstrated constant and proportional bias, with systematically higher absolute plasma NfL values measured by Lumipulse. Plasma and CSF NfL were significantly correlated within each platform (ρ=0.72 for Simoa; ρ=0.77 for Lumipulse). Lumipulse blood and CSF assays showed high precision. Across both platforms, plasma NfL increased with age and was higher in neurological disorders than in healthy controls.

Simoa and Lumipulse capture a consistent plasma NfL signal across neurological disorders, but absolute concentrations differ, supporting platform-specific, age-aware interpretation in clinical practice.