NEFL

NEFL

Overview

NEFL (neurofilament light chain, also abbreviated as NfL) is a cytoplasmic protein and a major structural component of neuronal intermediate filaments. As one of three neurofilament proteins (along with medium and heavy chains), NEFL is essential for maintaining axonal cytoskeletal integrity and normal neuronal function. When neurons undergo damage or degeneration, NEFL is released into the cerebrospinal fluid and subsequently into the bloodstream, where it can be quantified as a sensitive biomarker of neuroaxonal injury. This property has established NEFL as one of the most clinically relevant and increasingly implemented biomarkers in neurology, reflecting the degree of neuronal damage across multiple disease contexts.

NEFL functions as both a critical structural protein and as a disease-agnostic biomarker of neurodegeneration. Because neurofilament light chain levels in serum and cerebrospinal fluid correlate with the extent of neuroaxonal damage, measuring NEFL has become a powerful diagnostic, prognostic, and therapeutic response-monitoring tool in clinical neuroscience. Unlike disease-specific biomarkers, NEFL is applicable across numerous conditions—including neurodegenerative diseases, inflammatory neurological disorders, infectious diseases, and neuromuscular conditions—making it exceptionally valuable for assessing neurological disease activity and progression.

Recent Publications Focus

Below is a summary of the newest research publications targeting NEFL (sorted by publication date).

  • PMID: 42207242 — METABALS cohort, ALS prognosis This study examined neurofilament light chain as a prognostic biomarker in amyotrophic lateral sclerosis within the METABALS cohort, comparing it against inflammatory, metabolic, and central nervous system barrier biomarkers. The reported conclusion was that neurofilament light chain outperformed the other biomarker classes for prognosis, reinforcing its role as the only marker increasingly implemented in clinical practice for ALS risk stratification and outcome prediction. The work situates NEFL within a broader biomarker framework that included multivariate assessment of disease-relevant biological processes.

  • PMID: 42189430 — Temporal lobe epilepsy with comorbid depression In patients with temporal lobe epilepsy, with and without comorbid depression, serum neurofilament light chain was compared with glial fibrillary acidic protein and tau protein. Both the temporal lobe epilepsy with depression group and the temporal lobe epilepsy group had higher NfL levels than healthy controls, while no significant difference was observed between the two epilepsy groups. This pattern suggests that elevated NEFL-associated neuroaxonal injury is present in temporal lobe epilepsy, but the added presence of depression did not further distinguish NfL levels in this cohort. The study used statistical comparison with FDR correction to evaluate biomarker differences.

  • PMID: 41980534 — Hubei Memory and Aging Cohort Study This cohort study investigated how Folate and vitamin B12 relate to cognitive function through mediation models involving hemoglobin, homocysteine, and plasma Alzheimer’s disease biomarkers, including neurofilament light chain, Beta amyloid, and phosphorylated tau species. NEFL was included as part of a broader biomarker panel spanning neurodegeneration and metabolic status. The publication context indicates that chain mediation analyses were used to assess whether plasma biomarkers such as NFL contributed to the relationship between nutritional factors and cognition.

  • PMID: 42024828 — Emerging biomarkers in multiple sclerosis This review compared established biomarkers, especially neurofilament light chain and glial fibrillary acidic protein, with emerging candidates in cerebrospinal fluid and serum for multiple sclerosis. NEFL was presented as a benchmark biomarker for neuroaxonal injury, against which newer cytokines, proteins, and other candidates were evaluated. The article emphasizes the continued central role of NfL in multiple sclerosis biomarker research, particularly in relation to disease activity, treatment response, and central nervous system injury.

  • PMID: 41254882 — Acute HIV infection and immediate antiretroviral therapy This study measured neurofilament light, glial fibrillary acidic protein, and soluble triggering receptor expressed on myeloid cells 2 in cerebrospinal fluid collected during pre-antiretroviral acute HIV infection and at post-treatment visits extending up to 5 years. The design focused on neuroaxonal injury before and after immediate antiretroviral therapy, using longitudinal cerebrospinal fluid sampling to assess how early treatment influences biomarker trajectories. NEFL served as a key readout of neuronal injury in the context of acute HIV and treatment response.

  • PMID: 41237262 — Fingolimod-treated multiple sclerosis In fingolimod-treated multiple sclerosis, serum neurofilament light chain and Serum glial fibrillary acidic protein were evaluated as predictors of disease progression and relapse activity. The publication context indicates that serum NfL reflects both therapeutic response and insufficient or absent efficacy of disease-modifying therapy, while the longitudinal behavior of sGFAP as a marker for future progression independent of relapse activity was less clear. This study places NEFL in the context of treatment monitoring, using longitudinal models to relate biomarker dynamics to clinical outcomes under fingolimod.

  • PMID: 42412876 — Myasthenia gravis controlled cohort study This controlled cohort study assessed plasma neurofilament light chain and glial fibrillary acidic protein in myasthenia gravis. The authors describe the work as one of the larger controlled analyses incorporating both NfL and GFAP biomarkers in this disease, indicating an effort to define whether neuroaxonal injury markers are altered in myasthenia gravis and how they may complement clinical assessment. The study also referenced disease-specific clinical measures such as the Myasthenia Gravis Composite and the myasthenia gravis activities of daily living profile.

Across these publications, NEFL is consistently used as a marker of neuroaxonal injury in diverse neurological and neuroimmune disorders. The studies commonly pair neurofilament light chain with glial fibrillary acidic protein, inflammatory mediators, or barrier-related measures such as albumin quotient and blood-brain barrier permeability, and they use technologies including single molecule array, chemiluminescent immunoassay, linear mixed-effects models, multivariate models, and Cox proportional hazards analyses to relate biomarker levels to disease activity, prognosis, and treatment response.

Method PMIDs

  • [PMID 41254882]

Target PMIDs

  • [PMID 42207242]
  • [PMID 42189430]
  • [PMID 41980534]
  • [PMID 42024828]
  • [PMID 41237262]
  • [PMID 42412876]

Conclusion PMIDs

  • [PMID 42412876]