Same biomarker, different number: why multiple sclerosis needs assay-aware NfL interpretation

Blood neurofilament light chain (NfL) is moving from research into routine multiple sclerosis (MS) care, but the clinical meaning of a result depends partly on how that result was generated. Different specimen matrices and analytical platforms can preserve biological and clinical associations while producing non-interchangeable absolute concentrations. This matters particularly during longitudinal follow-up, where a platform change may mimic a biological change and affect interpretation near cut-offs or percentiles. We argue that analytical continuity should be treated as part of clinical continuity. NfL interpretation should explicitly integrate four domains-Biology, Method, Context and Action-and should prioritise patient-specific trajectories over isolated values. When possible, specimen matrix and analytical platform should be preserved; when the assay changes, the change should be documented and a new baseline considered. Making analytical metadata visible in the laboratory report is a practical step towards safer biomarker-guided neurology.