Serum neurofilament light chain correlates with myelin and axonal magnetic resonance imaging markers in multiple sclerosis.

BACKGROUND

Neurofilaments are cytoskeletal proteins that are detectable in the blood after neuroaxonal injury. Multiple sclerosis (MS) disease progression, greater lesion volume, and brain atrophy are associated with higher levels of serum neurofilament light chain (NfL), but few studies have examined the relationship between NfL and advanced magnetic resonance imaging (MRI) measures related to myelin and axons. We assessed the relationship between serum NfL and brain MRI measures in a diverse group of MS participants.

METHODS AND MATERIALS

103 participants (20 clinically isolated syndrome, 33 relapsing-remitting, 30 secondary progressive, 20 primary progressive) underwent 3T MRI to obtain myelin water fraction (MWF), geometric mean T (GMT), water content, T high angular resolution diffusion imaging (HARDI)-derived axial diffusivity (AD), radial diffusivity (RD), fractional anisotropy (FA); diffusion basis spectrum imaging (DBSI)-derived AD, RD, FA; restricted, hindered, water and fiber fractions; and volume measurements of normalized brain, lesion, thalamic, deep gray matter (GM), and cortical thickness. Multiple linear regressions assessed the strength of association between serum NfL (dependent variable) and each MRI measure in whole brain (WB), normal appearing white matter (NAWM) and T lesions (independent variables), while controlling for age, expanded disability status scale, and disease duration.

RESULTS

Serum NfL levels were significantly associated with metrics of axonal damage (FA: R = 0.29, R = 0.31, R = 0.30, R = 0.31; AD: R=0.31), myelin damage (MWF: R = 0.29, R = 0.30, RD: R = 0.32, R = 0.34, R = 0.30), edema and inflammation (T: R = 0.32; GMT: R = 0.31, R = 0.31), and cellularity (restricted fraction R = 0.30, R = 0.32) across the entire MS cohort. Higher serum NfL levels were associated with significantly higher T lesion volume (R = 0.35), lower brain structure volumes (thalamus R = 0.31; deep GM R = 0.33; normalized brain R = 0.31), and smaller cortical thickness R = 0.31).

CONCLUSION

The association between NfL and myelin MRI markers suggest that elevated serum NfL is a useful biomarker that reflects not only acute axonal damage, but also damage to myelin and inflammation, likely due to the known synergistic myelin-axon coupling relationship.