Neurofilament Light Chain

Neurofilaments, together with microtubules, form the neuronal cytoskeleton. They are exclusively located in neurons, especially large caliber axons. Neurofilaments are constantly released from neurons into the extracellular space and then into the cerebrospinal fluid (CSF).  CSF concentrations increase in individuals with neurodegeneration and neuronal injury. 

Neurofilament light chains (NfL) enter the bloodstream. In healthy individuals, plasma levels are about 2.5% of the levels in CSF. Plasma levels correlate highly with CSF concentrations. 

NfL concentrations in CSF and blood correlate with the degree of axonal damage in a variety of neurological disorders. Examples include traumatic brain injury, strokes, hereditary transthyretin-mediated amyloidosis, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson’s disease, frontotemporal dementia, Alzheimer disease, and Huntington disease. Serum NfL levels are higher in individuals with concussions.

Levels may be elevated in patients with stroke chronic kidney disease, atrial fibrillation, and myocardial infarction. 

Plasma NfL concentrations increase with age in healthy individuals. NfL levels in the blood of healthy controls increase by 2.2% per year between the ages of 18 years and 70 years. 

NfL is quantitated using an immunoassay. The preferred specimen is a red-top or lavender-top (EDTA) tube of blood. NfL concentration is 5-10% lower in plasma than in serum. Reference values are age and method dependent. 

References

Gaetani L et al. Neurofilament light chain as a biomarker in neurological disorders,
J Neurol Neurosurg Psychiatry, 2019 Aug;90(8):870-881.

Thebault S et al. Blood neurofilament light chain: The neurologist’s troponin? Biomedicines 2020;8:523.

Hviid CVB, Knudsen CS, Parkner T. Reference interval and preanalytical properties of serum neurofilament light chain in Scandinavian adults. Scand J Clin Lab Invest. 2020;80(4):291-295.

Khalil M, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018;14(10):577-589.