Neurofilament light (NfL) is a protein found within the nerve cells of the brain and spinal cord. It plays a significant role in maintaining the structural integrity of neurons. The presence of NfL outside these cells, particularly in bodily fluids, indicates neurological health. This protein’s recognition stems from its potential to reflect the state of nerve cells throughout the body.
Neurofilaments and Nerve Health
Neurofilaments are intermediate filaments, part of the cytoskeleton providing structural support to cells. Within neurons, these filaments are abundant in the axon, the long projection transmitting electrical signals. They function like structural beams, giving the axon its shape, strength, and stability. This internal scaffolding is important for the axon to maintain its cylindrical form and resist mechanical stress, enabling efficient signal transmission. The proper organization and function of neurofilaments are fundamental for the healthy operation of the nervous system.
Why Neurofilament Light is a Biomarker
Neurofilament light transitions from an intracellular structural protein to a detectable biomarker when nerve cells experience damage or degeneration. When a neuron’s axon is injured, its structural integrity is compromised, releasing NfL into the surrounding extracellular space. From there, NfL can diffuse into the cerebrospinal fluid (CSF), which bathes the brain and spinal cord. A portion of the NfL in the CSF can then cross the blood-brain barrier and enter the bloodstream, making it detectable through a blood test. Its presence in these biofluids acts as a measurable signal indicating neuronal injury or degeneration.
Conditions Linked to Elevated NfL
Elevated levels of neurofilament light are observed in various neurological conditions and injuries, reflecting ongoing nerve cell damage. In multiple sclerosis (MS), a chronic inflammatory disease affecting the central nervous system, NfL levels rise during active periods of demyelination and axonal loss. This indicates the direct destruction of nerve fibers characteristic of MS relapses and progression.
Neurodegenerative diseases also correlate with increased NfL. For instance, in Alzheimer’s disease, NfL levels gradually increase as neuronal degeneration progresses, reflecting widespread axonal damage. Patients with Parkinson’s disease, characterized by the loss of dopamine-producing neurons, often exhibit higher NfL concentrations, reflecting the neurodegenerative process.
Acute neurological events, such as traumatic brain injury (TBI) and stroke, also lead to significant NfL elevation. Following a TBI, mechanical forces cause immediate axonal shearing and disruption, leading to a rapid release of NfL into the CSF and blood. In stroke, the interruption of blood flow causes neuronal death and subsequent axonal damage, resulting in a measurable increase in NfL.
Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease affecting motor neurons, consistently shows elevated NfL levels, directly correlating with ongoing degeneration. Other conditions like Huntington’s disease, dementia with Lewy bodies, and some forms of peripheral neuropathy can also present with elevated NfL, underscoring its broad utility as a general marker of nervous system injury.
Measuring and Understanding NfL Levels
Neurofilament light levels are primarily measured through laboratory analysis of blood samples (serum or plasma) and cerebrospinal fluid (CSF). Blood tests for NfL are less invasive and more accessible, often utilizing highly sensitive techniques like single-molecule array (Simoa) technology to detect minute quantities of the protein. CSF analysis provides a more direct measure of NfL released within the central nervous system but requires a lumbar puncture.
While elevated NfL levels consistently indicate neuronal damage, interpreting these results requires careful clinical consideration. A high NfL value alone does not provide a specific diagnosis; instead, it signals that nerve injury is occurring. Clinicians integrate NfL results with a patient’s symptoms, medical history, neurological examination findings, and other diagnostic tests like MRI scans or genetic testing to form a complete picture. NfL is becoming a promising biomarker for monitoring disease progression, assessing treatment effectiveness, and predicting prognosis in various neurological conditions. However, it is not currently used as a standalone diagnostic tool, as its elevation is a general indicator of damage rather than a specific disease marker.