A biomarker is a measurable indicator that reveals something about a person’s biological state or condition. Think of it as a signpost for doctors, offering a glimpse into what is happening inside the body without invasive procedures. These markers, often molecules in blood or tissue, can signal disease, normal processes, or how the body is responding to treatment. Neurofilament light chain (NfL) has gained significant attention as an indicator of nerve cell injury.
What is Neurofilament Light Chain?
Neurofilament light chain is a protein that exists inside nerve cells, also known as neurons. Its purpose is to form part of the neuron’s internal support system within the long, slender projection called the axon. Neurofilaments are the most abundant structural proteins in neurons and are responsible for maintaining the axon’s diameter, which is important for the speed of nerve signal conduction.
These proteins assemble into long filaments, creating an internal network that functions much like a building’s scaffolding. This network provides structural integrity that gives the neuron its shape and helps it function correctly. NfL is the most abundant of these subunits, forming the backbone of the filament structure. In a healthy neuron, these proteins remain contained within the cell’s membrane.
How NfL Signals Nerve Damage
When a neuron is damaged by physical trauma, like a concussion, or by a neurological disease, its cell membrane can be compromised. This injury causes the axon’s internal scaffolding to break down, releasing its components, including NfL proteins. This release is a direct consequence of the axon losing its structural wholeness.
Once freed from the damaged cell, these NfL proteins leak into the cerebrospinal fluid (CSF), the liquid that bathes the brain and spinal cord. From the CSF, a small but measurable amount of NfL crosses the blood-brain barrier and enters the bloodstream. The presence of higher-than-normal NfL concentrations in either CSF or blood directly signals that nerve cell damage has occurred.
This mechanism makes NfL a useful, though not specific, marker for a wide range of neurological conditions. It is studied to assess brain injury in sports-related concussions. Tracking NfL is also valuable for monitoring disease progression in conditions like Multiple Sclerosis (MS), Alzheimer’s, and Amyotrophic Lateral Sclerosis (ALS).
The NfL Testing Process
NfL levels are measured using either a sample of cerebrospinal fluid or a blood sample. The traditional method involves a lumbar puncture, often called a spinal tap, to collect CSF directly from the area surrounding the spinal cord. This fluid provides a direct measurement of NfL and has been a reliable way to assess nerve injury.
While CSF analysis is direct, the procedure is invasive and not ideal for frequent monitoring. A major advancement is the development of ultra-sensitive blood tests that can detect the very low concentrations of NfL in the bloodstream. Technologies like the Single Molecule Array (Simoa) are sensitive enough to quantify these minute protein levels.
The ability to measure NfL in a simple blood test has made monitoring more practical and accessible. It allows for easier sideline assessments after a potential concussion or for more convenient, regular monitoring of patients with chronic neurological conditions to track disease progression and response to treatment.
Interpreting NfL Results
An NfL test does not provide a simple “yes” or “no” answer for a specific disease. Instead, the results are about quantity and change over time, which a doctor must interpret in a broader clinical context. Elevated NfL levels confirm neuronal injury has occurred, but the number itself does not identify the cause, as damage can result from many conditions.
Several factors must be considered. NfL levels naturally increase with age, so normal ranges are adjusted accordingly. For example, the range for a person aged 19-39 might be 2.47-7.25 pg/mL, while for someone aged 60-69, it could be 3.97-22.27 pg/mL. Body mass index (BMI) and kidney function also influence NfL concentrations.
A single measurement provides a snapshot, but tracking levels over time yields more valuable information. Observing NfL levels rise after an injury and fall during recovery can help monitor the healing process. In chronic diseases like MS, a drop in NfL levels can indicate that a therapy is successfully reducing nerve damage. The NfL test is one piece of a larger diagnostic puzzle.