Neurofilament light chain (NfL) is a protein that serves as a building block for the internal structure of nerve cells, or neurons. These cells are fundamental components of the brain, spinal cord, and the nerves extending throughout the body. Because the NfL protein is specific to neurons, its presence in bodily fluids can provide valuable information about the health of the nervous system.
The Structural Role of Neurofilaments
Within a healthy neuron, neurofilaments create an internal skeleton that is central to the cell’s form and function. This scaffolding provides structural support that helps maintain the neuron’s distinct shape, especially for the axon, the long, slender projection that transmits signals to other cells. The integrity provided by neurofilaments ensures the axon maintains its diameter, which affects the speed of nerve impulse conduction.
This internal framework also functions as a transport system within the cell. It facilitates the transport of materials, such as proteins and organelles, from the main body of the neuron down the entire length of the axon. This process, known as axonal transport, is necessary for keeping the distant parts of the neuron supplied. The neurofilament light chain is one of several protein subunits that assemble to form these larger neurofilament structures.
Assembled neurofilaments are stable structures inside the neuron. They belong to a family of proteins called intermediate filaments, which provide mechanical strength to cells. The light chain, along with medium and heavy chain proteins, polymerizes to create the final 10-nanometer diameter filaments that populate the axon. This construction ensures that neurons can withstand mechanical stress and maintain their elongated shape.
NfL as a Biomarker for Neuronal Damage
A biomarker is a substance that can be measured to provide insight into a particular biological state. Neurofilament light chain serves as a biomarker for damage to neurons. Because NfL is a protein found inside neurons, its presence in body fluids like cerebrospinal fluid or blood indicates that nerve cells have been compromised.
When a neuron’s axon is damaged or the cell itself degenerates, the outer membrane breaks down. This allows the internal contents of the cell, including the NfL proteins that form its cytoskeleton, to be released into the surrounding environment. These proteins first enter the cerebrospinal fluid (CSF), the liquid surrounding the brain and spinal cord, and can then pass into the bloodstream.
The concentration of NfL detected in a fluid sample corresponds to the extent of ongoing neuronal damage. A higher level of NfL suggests a greater rate of nerve cell injury or death. This allows clinicians to use NfL measurements as a dynamic indicator of disease activity. It is a non-specific marker, meaning elevated levels confirm neuroaxonal damage is occurring but do not identify the specific cause.
Clinical Applications in Neurological Conditions
The measurement of NfL is a tool for managing various neurological disorders. It offers insights into disease activity, progression, and treatment effectiveness. Its application varies by condition, providing distinct clinical information for each.
Multiple Sclerosis (MS)
In multiple sclerosis (MS), where the immune system attacks the protective sheath on nerve fibers, NfL levels reflect ongoing inflammatory damage. Elevated NfL concentrations can signal active disease, even without new symptoms, and may indicate a relapse is occurring. Monitoring these levels helps physicians assess if a treatment is effectively controlling the disease and reducing neuronal injury.
Amyotrophic Lateral Sclerosis (ALS)
For amyotrophic lateral sclerosis (ALS), a progressive disease affecting nerve cells in the brain and spinal cord, NfL is a prognostic indicator. Higher NfL concentrations in individuals with ALS are associated with more rapid disease progression and can help predict the rate of functional decline. While not used for diagnosis, tracking NfL provides information about the speed of motor neuron degeneration.
Alzheimer’s Disease and Other Dementias
In cognitive decline, NfL levels can help track the pace of neurodegeneration. For conditions like Alzheimer’s disease, elevated NfL correlates with the extent of brain cell damage and is associated with brain shrinkage (atrophy). While not specific to one type of dementia, its measurement can support a diagnosis of a neurodegenerative process and help differentiate it from other causes of cognitive symptoms.
Traumatic Brain Injury (TBI)
Following a traumatic brain injury (TBI) like a concussion, NfL levels provide an objective measure of the injury’s severity. The amount of NfL detected helps quantify the extent of axonal damage, offering more information than symptom-based assessments alone. This can be useful in guiding decisions about recovery and return-to-activity timelines.
How Neurofilament Light Chain is Measured
NfL concentrations are measured by analyzing bodily fluids, primarily cerebrospinal fluid or blood. The choice of fluid depends on the clinical context and the information being sought. Each method has distinct procedures and implications for the patient.
The traditional method is collecting cerebrospinal fluid via a lumbar puncture, or spinal tap. This procedure involves inserting a needle into the lower back to draw a sample of the fluid bathing the brain and spinal cord. Because NfL is released directly into the CSF, this method provides a direct measurement of neurodegeneration.
A more recent and less invasive approach is a standard blood test. NfL released into the CSF eventually enters the bloodstream, where it can be detected in plasma or serum. The development of highly sensitive testing technologies made this possible, as NfL concentrations in blood are much lower than in the CSF.
This technological advancement, particularly through platforms like the Single Molecule Array (Simoa), has transformed NfL testing. Simoa technology can detect minute quantities of the protein in a blood sample with a sensitivity older methods could not achieve. This has made routine monitoring more feasible, as a blood draw is simpler and more common than a lumbar puncture.