Neurofilament light chain (NFL) is a protein found within the nerve cells of the brain and spinal cord. It serves as an indicator of neuronal health and damage. Measuring NFL in bodily fluids provides insights into various neurological conditions, as its presence can signal underlying issues within the nervous system.
The Role of Neurofilaments in the Brain
Neurofilaments are structural proteins within neurons, the fundamental cells of the nervous system. They are often described as the “skeletons” of neurons, providing mechanical support and maintaining the shape of axons, the long, slender projections that transmit electrical signals. These protein polymers, measuring about 10 nanometers in diameter, are particularly abundant in large, myelinated axons and regulate axon diameter, influencing nerve impulse speed.
The nervous system contains four main types of neurofilament subunits: neurofilament light (NFL), neurofilament medium (NFM), neurofilament heavy (NFH), and alpha-internexin or peripherin. These subunits assemble in different combinations, forming complex networks within the neuronal cytoplasm. This internal scaffolding helps neurons maintain integrity and facilitates substance transport along the axon, contributing to overall nerve signal transmission.
NFL as a Biomarker of Neuronal Damage
NFL becomes a biomarker when neurons sustain damage or degenerate due to injury or disease. When the integrity of neuronal cells, particularly their axons, is compromised, neurofilaments break down. These NFL fragments are then released from neurons into the surrounding interstitial fluid.
From the interstitial fluid, NFL can enter the cerebrospinal fluid (CSF), which bathes the brain and spinal cord, and subsequently the bloodstream. Elevated NFL levels in these bodily fluids indicate ongoing neuronal injury or degeneration. This makes NFL a valuable, objective measure of nerve damage, offering insights that complement more subjective clinical symptoms.
Neurological Conditions Associated with Elevated NFL
Elevated NFL levels reflect widespread neuronal damage across various neurological conditions. In multiple sclerosis (MS), increased NFL concentrations in both CSF and blood are linked to disease activity, relapses, and disability progression. This indicates ongoing axonal damage, a hallmark of MS. Monitoring NFL levels can also assess the effectiveness of MS therapies.
In neurodegenerative diseases like Alzheimer’s (AD) and Parkinson’s (PD), elevated NFL levels indicate neuronal loss. For instance, in sporadic AD, NFL levels can begin to rise up to 10 years before clinical symptoms, and in familial AD, this increase may be seen as early as 22 years prior. While NFL is not specific to a single disease, its levels can help differentiate between conditions that cause neuronal damage and those that do not, even when symptoms appear similar.
Traumatic brain injury (TBI) and stroke also cause significant NFL release due to acute neuronal damage. Studies show NFL levels accumulate over days following such events and can remain elevated for months, reflecting injury extent. Amyotrophic lateral sclerosis (ALS) consistently shows elevated NFL levels, reflecting progressive motor neuron degeneration. Research suggests NFL levels in ALS can be elevated even in the presymptomatic phase, up to two years before clinical onset.
Measuring and Understanding NFL Levels
NFL levels are primarily measured through blood tests and cerebrospinal fluid (CSF) analysis. While CSF historically offered higher NFL concentrations, advancements in highly sensitive techniques, such as single molecule array (Simoa), have made blood-based measurements increasingly reliable and convenient. Simoa allows for detecting very low protein concentrations, and blood NFL measurements often correlate well with those in CSF.
Elevated NFL levels indicate ongoing neuronal damage, disease activity, or progression. For instance, higher NFL levels in MS patients correlate with greater long-term disability. This biomarker can also monitor treatment effectiveness; a decrease in NFL levels after therapy suggests reduced neuroaxonal damage. NFL is a general marker of neuronal damage, not a specific diagnostic tool for any single disease. Therefore, NFL results must always be interpreted by a medical professional in conjunction with other clinical findings, imaging results, and the patient’s overall medical history.