Blood Levels of Nerve Cell Protein Likely Marker of Brain Injury to Come

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by Forest Ray PhD |

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cxcl13 as MS biomarker

A nerve cell protein found in the blood shows potential as a biomarker of neuroinflammation and future neurodegeneration in the early stages of multiple sclerosis (MS), a study reports.

The protein, called serum neurofilament light chain (sNfL), is a known marker of injury to axons (nerve fibers).

These findings were reported in the study “Serum neurofilament light chain reflects inflammation-driven neurodegeneration and predicts delayed brain volume loss in early stage of multiple sclerosis,”  published in the Multiple Sclerosis Journal.

MS is a neurodegenerative autoimmune disease, in which the myelin sheath — which protects and insulates axons — is destroyed, leading to inflammation and nerve damage.

sNfL levels have been suggested as a potential MS biomarker, and studies have shown a strong correlation between its levels and both lesion burden and brain volume loss.

However, studies into the use of sNfL as a biomarker for disease activity and neurodegeneration in MS over the long term are lacking.

To assess this use of sNfL, an international team of researchers compared blood levels of this protein to brain imaging markers and other clinical measures in 172 patients (mean age, 29) in the early stages of MS.

Patients were clinically examined every three months over the course of three years (36 months), and underwent brain magnetic resonance imaging (MRI) scans every year.

Results showed a strong relationship between sNfL levels and both T1 and T2 MRI lesion volume (measurements of areas of active inflammation [T1] and of total damaged nervous tissue [T2] — both old and new — in the brain), as well as the total number of brain lesions.

sNfL levels also appeared predictive of neurodegeneration associated with a delayed, but not immediate, brain volume loss.

“There was no relationship between percentage changes of sNfL and brain volume loss over 36 months,” but “early sNfL levels were associated with delayed brain volume loss after 48 months,” the researchers wrote.

This suggested that early damage to axons could have a large impact on neurodegeneration over time.

Data also suggested that a patient’s sNfL levels reflected their disease status. Patients with no evidence of disease activity, a status known as NEDA-3, had lower sNfL levels than did those with active disease. Patients whose symptoms became active within 36 months of initial testing showed higher sNfL levels over follow-up visits than did those who remained on NEDA-3 status.

“sNfL is associated with ongoing neuroinflammation and predictive of future neurodegeneration in early MS,” the researchers concluded.

Specifically, “increased levels of sNfL in early MS stages reflects neuropathological processes driven mainly by ongoing neuroinflammation as indirectly assessed by the accumulation of lesion burden. In addition, sNfL levels have a stronger association with future development of brain atrophy than with actual or previous brain volume loss,” the team added.

Based on these results, the researchers believe that sNfL may qualify as a biomarker of MS disease activity and as an endpoint in clinical trials.

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