Areas of clinical study for neurofilament light chain

Various pathologies can cause axonal damage—making it important to have a simple, affordable biomarker to quickly and accurately assess and monitor neuronal injury and neurodegeneration.

What Are Neurofilaments?

Neurofilaments are cell-specific structural proteins found in abundance in the axonal interior of healthy, myelinated neurons¹ (Figure 1). They are composed of heavy, medium and light chain components that form heteropolymers to facilitate axonal diameter determination and facilitate attachment by organelles.² Neurofilaments are constantly released from neurons into the extracellular space and make their way into the cerebral spinal fluid (CSF) and peripheral blood, providing for a basal level of detectable neurofilament light chain proteins in both CSF and blood. Serum NfL (sNfL) levels in healthy individuals are lower than those in CSF but correlate.³ New technologies have enabled NfL to be reliably measured in plasma and serum.⁴ Levels of sNfL rise above normal in response to neuronal injury and neurodegeneration independent of cause, making its potential utility as a biomarker both obvious but also inherently context dependent on clinical assessment.
 

Figure 1: Neurofilament light chain is a neuron specific protein that lines the axons of healthy neurons.

Areas of Clinical Study for NfL

NfL has been studied as a neurodegenerative or neuronal injury biomarker in a variety of diseases and conditions,³ including: 

• Multiple Sclerosis (MS): sNfL has been widely studied as a marker of disease progression, treatment efficacy, and clinical outcomes for MS.³ sNfL levels are increased in early relapsing MS and have been shown to correlate with markers of disease severity.⁵ Treatment with disease-modifying therapy has been reported to be associated with lower sNfL levels compared to untreated individuals.⁶ A key challenge with having more definitive clinical guidance for sNfL in MS patients had been the lack of wide availability of an sNfL assay.
• Alzheimer’s Disease (AD): The application of sNfL as a potential biomarker for AD has been extensively investigated.^3,7-10 Elevated NfL levels have been associated with the presence of beta- amyloid plaques in pre-symptomatic individuals and with the level of tau in symptomatic patients.⁹ Additionally, elevated sNfL levels can be a predictor of disease progression in symptomatic patients with subjective cognitive decline.¹⁰
• Huntington’s Disease (HD): sNfL levels were significantly higher in patients with HD than in healthy controls,¹¹ and increased sNfL levels were found in young adult carriers of HD gene mutation years before the clinical onset of symptoms.¹²
• Parkinson’s Disease: sNfL levels have been shown to correlate with disease severity and motor and cognitive decline.^13,14
• Amyotrophic Lateral Sclerosis (ALS): sNfL levels can have diagnostic and prognostic value for symptomatic patients¹⁵ and distinguish early-onset ALS patients from those with other neurologic diseases.¹⁶
• Spinocerebellar Ataxias: NfL can help stratify pre-ataxic individuals with regard to onset and facilitate early detection of neurodegeneration.¹⁷
• Concussion recovery: NfL can be used, in conjunction with clinical observation, as a primary biomarker to assess “return to play” in athletes with sports-related concussion.^18-20
• Oncology: Use of NfL testing prior to immunotherapy infusions may permit for early identification of patients at risk for immune effector cell-associated neurotoxicity syndrome.²⁶

Reference Intervals

NfL levels in healthy patients are known to generally increase with age throughout adulthood.^21,22 Younger children have higher NfL levels than older children reaching a nadir between the ages of 10 and 15 years, then increasing in a linear fashion until the age of 60 years and accelerating non-linearly thereafter.^22-24 Also, a WHO or other appropriate standard for NfL does not yet exist. For these reasons, Labcorp generated de novo reference intervals by measuring a total of 1,634 samples from individuals representing the range of ages mentioned above. Because the disease state indication is increased NfL levels, only an upper reference interval value is employed (Table 1).

Labcorp offers

• Neurofilament Light Chain, Plasma (140555)
• Neurofilament Light Chain, Serum (140455)