Neurofilament Light Chain Blood Test Normal Range Explained

The nervous system’s fundamental units are nerve cells, or neurons. Scientists have identified a protein called neurofilament light chain (NfL) as a component of these cells. When neurons are damaged, NfL proteins are released into the body’s fluids, including the bloodstream. A blood test has been developed to measure the concentration of this protein, offering a window into the health of the nervous system and providing information about potential nerve cell injury.

The Role of Neurofilament Light Chain in Nerve Health

Neurofilaments are proteins that form the internal scaffolding, or cytoskeleton, of neurons. This structure is important in the axon, the long projection of a nerve cell that transmits information. These filaments provide support and help maintain the axon’s diameter, which allows for efficient conduction of nerve impulses. Neurofilament light chain (NfL) is the most abundant of these neurofilament proteins.

When a neuron’s axon is damaged due to injury or disease, its framework breaks down, releasing NfL proteins. These proteins first enter the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord. From the CSF, a small amount of NfL makes its way into the bloodstream.

Because NfL is specific to neurons, its presence in the blood is a direct indicator of neuroaxonal damage. The concentration of NfL in a blood sample can reflect the extent of this damage, making it a valuable biomarker—a measurable substance indicating a specific biological state. Even healthy individuals have a low, baseline level of NfL in their blood due to the normal turnover of proteins within neurons.

How the NfL Blood Test Works

The neurofilament light chain test is performed on a blood sample obtained from a simple vein draw. This makes the test non-invasive and allows for repeated measurements over time to monitor changes in nervous system health. Its accessibility is a significant advantage compared to analyzing cerebrospinal fluid, which requires a lumbar puncture.

Since NfL is present in the blood at extremely low concentrations, highly sensitive laboratory techniques are required. One of the most common methods is the Single Molecule Array (Simoa) technology, an ultra-sensitive immunoassay capable of detecting single molecules of the NfL protein. Other methods like ELISA (Enzyme-Linked Immunosorbent Assay) may also be used.

The test result measures NfL concentration in the blood, reported in picograms per milliliter (pg/mL). This quantitative value can then be compared against established reference ranges.

Defining Normal Neurofilament Light Chain Levels

A single, universal “normal” value for NfL does not exist. Instead, typical levels are determined by reference ranges created from measuring NfL concentrations in large, healthy populations. These ranges account for what is standard across different groups.

The most significant factor influencing NfL levels is age. As a person gets older, their NfL levels naturally and gradually increase. This means the expected normal range for a 25-year-old is considerably different from that of a 70-year-old, reflecting subtle changes in the nervous system over a lifetime.

Other factors can also affect NfL concentrations, including:

• The specific laboratory assay and testing platform used.
• An individual’s body mass index (BMI).
• Conditions that affect protein clearance, such as impaired kidney function.

Because of these variables, a healthcare provider must interpret test results in the context of a patient’s personal health profile and the laboratory’s specific reference values.

What Elevated NfL Levels Indicate

An NfL level is considered elevated when it is higher than the established reference range for an individual’s age group. An elevated result suggests active or recent damage to the axons of neurons, serving as a general indicator of neurological stress or injury.

NfL is a non-specific biomarker of neuroaxonal injury. This means that while an elevated level indicates neuronal damage has likely occurred, the test itself does not identify the underlying cause. Many different conditions can lead to an increase in NfL, from chronic diseases to acute events like a head injury.

An elevated NfL level is not a standalone diagnostic tool for any specific disease. Physicians interpret the result alongside a patient’s symptoms, medical history, neurological examination, and other diagnostic tests like magnetic resonance imaging (MRI). The test provides a quantitative measure of neuronal damage that helps guide further investigation.

NfL Testing in Neurological Conditions

The NfL test’s ability to detect neuroaxonal damage makes it a valuable tool in the management of various neurological disorders. Its applications are found in inflammatory conditions, neurodegenerative diseases, and acute injuries.

Multiple Sclerosis (MS)

In MS, a condition characterized by inflammatory damage to the nervous system, NfL levels can help monitor disease activity. The test can also assess how well a treatment is working. A drop in NfL levels after starting a new therapy may suggest it is effectively reducing nerve damage.

Neurodegenerative Diseases

For diseases such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS), elevated NfL levels can reflect the rate of ongoing neuronal loss. In these conditions, the test can aid in prognosis and help track disease progression. For instance, in ALS, higher NfL levels have been correlated with a faster rate of disease progression.

Acute Neurological Injuries

The test is also useful in assessing acute injuries. Following a traumatic brain injury (TBI) or concussion, NfL levels can help gauge the severity of the injury and monitor the recovery process. Similarly, after a stroke, NfL can serve as an indicator of neuronal damage. In all applications, the NfL test is used as part of a comprehensive evaluation by healthcare professionals, with ongoing research continuing to refine its clinical role.