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ACTRIMS 2023 | Interpretation of serum NfL depends on the selection of a reference population

Blood neurofilament light chain (NfL) is an emerging biomarker of neurological diseases, including multiple sclerosis (MS). However, it is crucial to establish normal reference intervals. One of the challenges is that age heavily influences NfL levels; therefore, age-specific reference ranges for blood NfL are required. Elias Sotirchos, MD, Johns Hopkins University School of Medicine, Baltimore, MD, describes an ongoing study examining the agreement between published reference methods for NfL applied to a large population of people with MS. NfL was measured in 12,730 blood samples from 6,635 individuals with MS. Six published reference populations were used to classify NfL as elevated or normal. NfL values were classified as elevated if they exceeded the upper limit of the age-specific reference range. Depending on the selection of the reference population, the proportion of NfL measurements classified as elevated varied from 3.7% to 30.9%. These results raise the importance of caution in interpreting single NfL values and accounting for additional factors, including comorbidities. This interview took place at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023 in San Diego, CA.

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Elias Sotirchos reports scientific advisory boards and/or consulting for Alexion, Viela Bio, Horizon Therapeutics, Genentech and Ad Scientiam; speaking honoraria from Alexion, Viela Bio and Biogen.