Neurofilament light chain (NfL) measurement has emerged as a key biomarker for the diagnosis, monitoring, and prediction of neurologic disorders in recent years.

The Spanish Society of Fibromyalgia and Chronic Fatigue Syndrome reported that NfL measurements help detect neuroaxonal injury in conditions such as multiple sclerosis (MS), Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and traumatic brain injury.

Analysing NfL levels in cerebrospinal fluid (CSF) via lumbar puncture or in blood using ultrasensitive assays is a major step toward clinical application.

Measuring serum NfL levels may enable clinicians to assess disease activity, predict progression, and monitor treatment response, supporting more individualised and timely therapeutic decisions.

Neurofilament Evidence

A study published in Revista Clínica Española analysed data from 1751 adults in the 2013-2014 National Health and Nutrition Examination Survey.

Higher serum NfL levels were significantly associated with a greater risk for depression, stroke, subjective memory deficits, and longer sleep duration (P < .05).

BMI also influences the relationship between serum NfL levels and subjective memory deficits.

Similarly, JAMA Psychiatry reported elevated NfL concentrations in the CSF or blood of patients with behavioural variant frontotemporal dementia, a neurodegenerative disorder with prominent neuropsychiatric symptoms.

In the Journal of Neurology, a study involving 27 patients with post-COVID linked olfactory impairment to increased serum NfL, suggesting its potential as a biomarker of brain injury in both the acute and postacute stages of SARS-CoV-2 infection.

Clinical Role

The Spanish Society of Laboratory Medicine describes neurofilaments as neuron-specific intermediate filament proteins that, together with actin filaments and microtubules, form the cytoskeleton of neurons.

Neurofilaments are concentrated primarily in myelinated axons, where they maintain axonal diameter and ensure rapid conduction of nerve impulses.

Neurofilament proteins consist of several subunits, including NfL, which can be detected in the serum using immunoassays. Serum NfL levels show a strong correlation with CSF concentrations, allowing clinicians to monitor disease activity through a simple blood test.

Serum NfL measurement may reduce the need for lumbar punctures and imaging procedures.

However, because serum NfL levels increase in response to various types of neuroaxonal injury, this marker lacks diagnostic specificity and should not be used alone for diagnosis.

Expert Insights

During the conference “Biomarkers: The Value of a Multidisciplinary Approach in Neurological Pathologies,” organised by Siemens Healthineers, experts in immunology, neurology, and biochemistry highlighted NfL as a major advancement in clinical neurology for monitoring patients with diseases such as MS.

Luis Querol, MD, from the Neuromuscular Diseases Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, confirmed, “Although neurofilament light chains are applied in degenerative diseases, they are also useful in acquired and traumatic conditions.

They can anticipate the diagnoses of disorders such as ALS, MS, and transthyretin amyloidosis and help distinguish between good and poor treatment responses. They are a predictor of the future that lets us make therapeutic decisions earlier.

Clinical biochemist José Ángel Noval, from the Immunoproteins, Tumor Markers, and Neurobiochemistry Unit at Virgen del Rocío University Hospital, Seville, Spain, noted that neurofilaments “could be the PCR [polymerase chain reaction] of neurology.” Monitoring neurofilaments in MS and ALS “is a game changer.”

He emphasised that implementing NfL testing requires careful management of preanalytical, analytical, and postanalytical factors and confirmed that neurofilaments are stable and reproducible.

The forum addressed several key challenges in implementing NfL as a biomarker, including assay standardisation, traceability, reduction of interlaboratory and methodological variability, availability of certified reference materials, and uniform measurement procedures.

Experts have highlighted the need for appropriate technology, professional training, and updated clinical guidelines to support the routine use of these biomarkers in clinical practice.

During the meeting, Eddine Merabet, head of Assay Technology Innovation (R&D), Siemens Healthineers, presented the “Atellica NfL” assay, intended for in vitro diagnostic use for the quantitative measurement of NfL in human serum and plasma (ethylenediaminetetraacetic acid), using the “Atellica IM” and “ADVIA Centaur” systems, which are useful for identifying adults with relapsing-remitting MS.

Combined with clinical and imaging data, the assay can help identify adult patients with relapsing-remitting MS at an increased risk for disease activity, defined by the appearance or increase in T2 lesions on MRI over a 2-year period.

Merabet also noted Siemens Healthineers’ ongoing development of new biomarkers to help neurologists diagnose and monitor Alzheimer’s disease.

These include phosphorylated tau 217 (p-tau 217) and brain-derived tau. He added that glial fibrillary acidic protein will be incorporated to complete the biomarker panel for patients with MS.

The author declared having no conflicts of interest.

This story was translated from El Medico Interactivo.