Neurofilament light chain (NfL) is a structural protein found in neurons that is crucial for the maintenance and function of the cytoskeleton. It becomes detectable in serum and cerebrospinal fluid (CSF) when neural cells are damaged or degenerate. As such, NfL levels are emerging as a significant biomarker for various neurological diseases, reflecting the extent of neuronal injury or degeneration. Measurement of NfL in serum offers a less invasive method than CSF sampling, providing a practical approach for both clinical trials and potentially routine monitoring of neurodegenerative diseases.
Neurofilaments are neuron-specific intermediate filaments composed of light, medium, and heavy chains; NfL is the light chain component. These filaments are integral to the internal support structure of axons, providing the necessary framework that influences neuronal caliber and signaling speed. When neurons are damaged through injury or disease, fragments of NfL are released into the extracellular space and subsequently into the bloodstream, making serum NfL a valuable marker of neuroaxonal injury.
Elevated levels of NfL in serum have been correlated with several conditions, including:
Multiple Sclerosis (MS): In MS, NfL levels are associated with disease activity and progression. Monitoring NfL can help assess the efficacy of disease-modifying therapies and may predict future disease activity. Elevated NfL levels in MS patients often indicate active inflammation and ongoing neurodegeneration.
Amyotrophic Lateral Sclerosis (ALS): ALS patients show significant increases in serum NfL, reflecting the disease's rapid neurodegeneration. NfL levels can aid in prognosis and are potentially useful in evaluating responses to investigational treatments.
Alzheimer’s Disease (AD) and Other Dementias: NfL levels are elevated in Alzheimer’s disease and correlate with the severity of cognitive decline. Importantly, NfL can distinguish AD from other neurodegenerative diseases and may serve as a marker to monitor disease progression or the efficacy of therapeutic interventions.
Traumatic Brain Injury (TBI): Following TBI, serum NfL levels rise in proportion to the severity of injury. This makes NfL a valuable marker for assessing neuronal damage in acute settings and potentially predicting long-term outcomes.
Parkinson’s Disease (PD) and Related Disorders: Elevated NfL levels are observed in Parkinson’s disease and are exceptionally high in atypical Parkinsonian disorders. This helps in differentiating PD from other Parkinsonian syndromes, which is often challenging clinically.
Serum NfL is measured using highly sensitive immunoassays, such as ELISA or, more commonly, single-molecule array (Simoa) technology, which can detect extremely low concentrations of proteins. These advanced techniques have enabled the quantification of NfL in peripheral blood, making it accessible for routine clinical use.
The measurement of serum NfL provides a window into the neurodegenerative process across a spectrum of neurological diseases, offering a non-invasive biomarker of neuronal damage. Its application spans diagnostic clarification and disease monitoring to evaluating therapeutic efficacy in clinical trials.
