The Neurofilament Light Chain (NfL) blood test is an accessible tool for assessing nervous system health. NfL is a protein released into the bloodstream when nerve cells are damaged, acting as a biological marker of neurological injury. This simple, non-invasive blood test measures the extent of damage occurring in the central and peripheral nervous systems. Understanding the test requires knowing what NfL is, what its concentration signifies, and how medical professionals interpret the “normal range” for this biomarker.
The Role of Neurofilament Light Chain
Neurofilament Light Chain is a structural protein found exclusively within neurons, the specialized cells of the nervous system. NfL is one of the three main subunits forming neurofilaments, which function as the internal scaffolding, or cytoskeleton, of the neuron. These neurofilaments are particularly concentrated in the axon, the long, slender projection that transmits electrical impulses to other cells.
These structures maintain the neuron’s shape and provide mechanical stability, especially to the vulnerable axons. Neurofilaments also help regulate the axon’s diameter, which determines the speed at which nerve signals travel. The structural integrity provided by these proteins is essential for the continuous, healthy functioning of the nervous system.
What Elevated NfL Levels Indicate
When a neuron is injured or begins to degenerate, the structural integrity of its axon is compromised, causing the NfL protein to spill out. This released NfL first enters the cerebrospinal fluid (CSF) surrounding the brain and spinal cord, and then crosses into the bloodstream, where it can be measured. Elevated NfL levels in the blood therefore serve as a general indicator of recent or ongoing damage to nerve cells.
Because NfL is present in almost all neurons, its elevation confirms the presence of neuro-axonal injury rather than pointing to a specific disease. A high level indicates that a significant amount of nerve cell damage is occurring somewhere in the nervous system. This universal response makes NfL a valuable marker for monitoring overall nervous system health, whether the damage is acute (like a concussion) or chronic (as seen in neurodegenerative conditions).
Defining the NfL Normal Range
Defining a single, universal “normal range” for the Neurofilament Light Chain blood test is complicated and often misleading. NfL concentration is reported in picograms per milliliter (pg/mL), an extremely small measurement reflecting its low concentration in healthy individuals. The primary factor influencing the normal baseline is a person’s age, as NfL levels naturally increase throughout a lifetime.
For example, a healthy person in their 20s might have a normal NfL concentration below 10 pg/mL, while a healthy person in their 70s could have an upper limit exceeding 20 pg/mL. This age-related increase means results must be interpreted against age-matched reference ranges developed from large cohorts of healthy individuals. Laboratories typically provide results as a percentile or Z-score relative to people in the same age bracket to account for this change.
A second complexity is measurement variability, as different laboratory assays can produce different absolute values. Highly sensitive single-molecule array (Simoa) technology has enabled blood-based testing, but its results are not directly interchangeable with older methods like ELISA. Consequently, each testing facility must validate and use its own specific reference ranges based on the exact assay and equipment employed. A result considered elevated on one platform might be normal on another, reinforcing the need for interpretation by a specialized medical provider.
Clinical Applications of NfL Testing
The primary utility of NfL testing lies in monitoring disease activity and the effectiveness of treatments. In conditions like Multiple Sclerosis (MS), consistently elevated NfL levels indicate ongoing nerve damage, even without new physical symptoms. Measuring NfL over time helps physicians track disease progression and adjust therapy, as a decrease suggests a positive response to treatment.
NfL testing is also valuable in neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s disease. In ALS, NfL levels correlate with the speed and severity of disease progression, offering prognostic information. For acute events like Traumatic Brain Injury (TBI) or stroke, NfL helps assess the initial severity of axonal damage and predict longer-term recovery outcomes. NfL also serves as an objective biomarker in clinical trials, providing a measurable endpoint to determine if a new drug is successfully slowing nerve cell injury.