Neurofilament Light Chain, Plasma

EDTA plasma

1 mL

0.7 mL (Note: This volume does not allow for repeat testing.)

Lavender-top (EDTA) tube

This test is used for the measurement of the level of Neurofilament Light Chain in plasma.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

There are significant variations in measured plasma NfL levels among different methods and labs. Care must be taken when interpreting results obtained in different studies.

Direct comparisons of absolute values can only be done on the same source fluid (plasma or serum).¹

A rise in NfL is not specific for a specific disease factor and may be caused by both neurodegenerative diseases or a head impact during sports. Results should only be used in conjunction with other clinical information when evaluating patients with neurodegeneration. Due to a lack of specificity to a particular neurodegenerative disease, its role as a diagnostic marker is limited.

There are numerous demographic, life style, and comorbidity factors that potentially influence NfL levels in plasma. Variables such as exercise,² blood volume, body mass index may impact measured plasma NfL levels.

NfL levels measured in the morning are more than 10% higher than those measured in the evening.^3,4

Caution should be taken in interpreting NfL levels when disease treatment induced neurological complications that can potentially impact NfL levels.^5,6

Plasma NfL levels can be decreased in patients with high immunoglobulin G (IgG) levels.

Higher concentrations of NfL may be found in persons with history of stroke, atrial fibrillation, myocardial infarction, chronic kidney disease, pregnancy, and diabetes.

Lower concentrations of NfL may be found in individuals who are obese (BMI > or =30).

Roche Diagnostics Electrochemiluminescence Immunoassay (ECLIA)

See table.

Neurofilament proteins are protein polymers measuring 10 nm in diameter and many micrometers in length that, together with microtubules and microfilaments, form the neuronal cytoskeleton.^7,8 These proteins are also prominent components of abnormal intra-neuronal aggregates in varied neurodegenerative diseases, including multiple sclerosis (MS), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Huntington disease (HD).⁹ Neurofilament light chain (NfL) is constantly released from neurons into the extracellular space and ultimately reaches the cerebrospinal fluid (CSF) under physiological conditions. CSF NfL concentrations can increase in neurodegeneration and neuronal injury across a wide range of neurologic diseases. Plasma NfL (pNfL) levels in healthy individuals are about 2.5% of the levels in CSF and correlate highly with the concentrations in CSF.^1,10-14 pNfL levels rise above normal in response to neuronal injury and neurodegeneration independent of cause.¹⁵

pNfL levels are increased in early relapsing multiple sclerosis (MS) and have been shown to correlate with markers of disease severity.^3,10,16-24 In some reports, pNfL has been able to detect MS disease activity earlier than routine MRI²⁵ and before clinical MS onset of disease.^17,26,27 In patients with confirmed relapsing or progressive MS, pNfL can predict short-term outcomes including clinical and cognitive performance^10,17,22,28 as well as predicting long-term worsening and risk of developing progressive MS.²⁹ Treatment with disease modifying therapy has been reported to be associated with lower pNfL levels compared to untreated individuals.^{10,17,18,25,30,31} Increased pNfL levels can indicate neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis.⁵

The application of pNfL as a potential biomarker for Alzheimer's disease (AD) has been extensively investigated.^9,11,32-39 pNfL levels have been shown to be higher in patients with mild cognitive impairment and patients with AD compared with healthy controls.^40,41 Moreover, higher pNfL levels have been associated with cognitive decline in non-dementia older adults.⁴² Elevated NfL levels have been associated with the presence of amyloid-beta plaques in pre-symptomatic individuals and with the load of tau in symptomatic patients.³⁶ Increased pNfL levels have also been associated with AD progression independent of amyloid-beta.⁴³ pNfL levels have been shown to correlate with Braak staging in AD⁴⁴ and normal pNfL levels have been linked with resistance to PS1 familial AD in apolipoprotein E3 (APOE3) Christchurch mutation.⁴⁵

In amyotrophic lateral sclerosis (ALS), elevated pNfL levels have been observed up to 3.5 years before symptom onset with the extent to which the elevation of NfL occurs prior to symptoms related to the specific gene mutation causing the disease.^46,47 Levels of NfL have been shown to have excellent diagnostic and prognostic performance for symptomatic patients with ALS.^48-52

pNfL levels reflect cortical neurodegeneration from the very early stages of Parkinson's disease (PD) and have been shown to track the underlying pathological process leading to PD dementia.^16,53-59 Higher baseline NfL levels were also associated with greater motor and cognitive decline after a follow-up period of 3 years in patients with PD.^16,54,55 pNfL levels correlated with disease severity and levels reflect cortical neurodegeneration from the very early stages of PD.⁵⁴ In advanced PD patients, pNfL concentrations are associated with motor function, cognitive decline and subclinical cardiac damage.⁶⁰

In HD, pNfL levels were significantly higher in patients than in healthy controls and significantly higher in manifest HD than pre-manifest HD.^61-63 Increased pNfL levels were found in young adult carriers of HD gene mutation approximately 24 years before the clinical onset of symptoms.⁶⁴

In frontotemporal dementia (FD), pNfL levels were found to be significantly higher than in healthy controls with the elevations correlating with disease severity.⁶⁵ Increased pNfL levels were observed 1 to 2 years before the clinical onset of symptoms in patients with FD.⁶⁶ In patients diagnosed with dementia with Lewy bodies (DLB), pNfL levels were found to be about 2-fold higher than in healthy controls with the elevations correlating with disease severity.⁶⁷ pNfL levels were found to be a superior predictor of cognitive decline compared to age, sex and baseline severity variables in DLB.⁶⁷ In patients with Charcot-Marie-Tooth neuropathy, pNfL levels were about 2-fold higher in patients than in healthy controls and levels correlated with disease severity.^68-70 pNfL levels were also found to be significantly elevated in acquired peripheral neuropathy with levels that correlated not only with disease severity but also with outcome.⁷¹ pNfL levels also declined with remission.⁷²

Increased levels of pNfL have been reported in patients with traumatic brain injury (TBI).^73-77 pNfL levels are higher in all patients suffering from concussion compared to healthy controls. Sports-related concussion has specifically been associated with higher levels of pNfL.⁷⁷

In the acute and post-acute phase after stroke, high pNfL levels are associated with poor clinical outcome and positively correlate with secondary neurodegeneration as assessed by MRI.⁷⁸

Hereditary transthyretin-mediated (ATTRv) amyloidosis: NfL has been studied as a biomarker for the polyneuropathy (PN) caused by ATTRv amyloidosis. Plasma and serum NfL levels are increased in patients with the PN of ATTRv amyloidosis and have been demonstrated to correlate with disease severity.^79-83 Treatment with therapeutics targeting ATTRv amyloidosis has been reported to decrease NfL levels significantly, while an increase was observed in placebo-treated patients.^79,84