Neurofilament light chain: a biomarker at the crossroads of clarity and confusion for gene-directed therapies

Neurodegener Dis Manag. 2024 Nov 15:1-13. doi: 10.1080/17582024.2024.2421738. Online ahead of print.

Abstract

Neurofilament light chain (NfL) is a promising biomarker for neurodegenerative diseases, measurable in both CSF and blood upon neuroaxonal damage. While CSF analysis was traditionally used, blood-based assays now offer a less invasive alternative. NfL levels correlate with disease severity and progression in conditions like Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis and Huntington's disease. Clinical trials demonstrate its utility as a pharmacodynamic biomarker in MS and ALS. The FDA's approval of Tofersen for SOD1-ALS based on NfL reduction underscores its growing acceptance as surrogate marker. However, challenges remain in standardizing assays, interpreting clinical correlations, low specificity and understanding the dynamics between CSF and blood NfL levels. Addressing these issues is crucial for maximizing NfL's potential in neurodegenerative disease management.

Keywords: Alzheimer's disease; Huntington's disease; amyotrophic lateral sclerosis; gene-directed therapies; multiple sclerosis; neurodegenerative diseases; neurofilament light chain.

Plain language summary

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Publication types

  • Review