Neurofilaments and Beyond: Multi‑Modal Biomarkers and the Hidden Biology of ALS
DOI:
https://doi.org/10.18192/osurj.v5i1.7924Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive upper and lower motor neuron loss and death from respiratory failure within a few years of symptom onset. The marked clinical and biological heterogeneity of ALS has hindered the development of effective therapies, prompting intense interest in biomarkers that can improve diagnosis, prognostication, and trial efficiency. This review summarizes recent advances in fluid, imaging, genetic, and digital biomarkers of ALS, with a particular focus on neurofilament light chain as a leading candidate for prognostic and pharmacodynamic use. It highlights how current biomarkers, while promising, remain imperfect surrogates for underlying disease biology, and often expose fundamental gaps in understanding ALS pathogenesis. It argues that to fully realize the potential of biomarkers, the field must invest more heavily in mechanistic and longitudinal research that links biomarker dynamics to cellular pathways, genetics, and patient outcomes, ultimately enabling more rational, personalized therapeutic strategies.
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