Multidimensional overview of neurofilament light chain contribution to comprehensively understanding multiple sclerosis

Abstract

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease characterized by demyelination, progressive axonal loss, and varying clinical presentations. Axonal damage associated with the inflammatory process causes neurofilaments, the major neuron structural proteins, to be released into the extracellular space, reaching the cerebrospinal fluid (CSF) and the peripheral blood. Methodological advances in neurofilaments’ serological detection and imaging technology, along with many clinical and therapeutic studies in the last years, have deepened our understanding of MS immunopathogenesis. This review examines the use of light chain neurofilaments (NFLs) as peripheral MS biomarkers in light of the current clinical and therapeutic evidence, MS immunopathology, and technological advances in diagnostic tools. It aims to highlight NFL multidimensional value as a reliable MS biomarker with a diagnostic-prognostic profile while improving our comprehension of inflammatory neurodegenerative processes, mainly RRMS, the most frequent clinical presentation of MS.

NfL concentration in CSF is a quantitative marker of the rate of neurodegeneration in aging and Huntington's disease: a semi-mechanistic model-based analysis

“…Neurofilament light chain (NfL), a 61.5 kDa structural protein exclusive to neurons, combines with medium and heavy chain (NfM and NfH) neurofilaments to form type IV intermediate fibers (Khalil et al, 2018 ). Upon axonal damage or neuronal death, NfL is released to the extracellular space where it is removed via microglia- and CSF-mediated mechanisms (Khalil et al, 2018 ; Kölliker Frers et al, 2022 ). The concentrations of NfL in cerebrospinal fluid (CSF) and plasma are purported markers of neurodegeneration in a number of neurological diseases (Khalil et al, 2018 ; Gaetani et al, 2019 ).…”