Netherlands Institute for Neuroscience
Neuro-immunology

Author Of 1 Presentation

Biomarkers and Bioinformatics Poster Presentation

P0119 - Neurofilament light chain levels correlate with lesion activity and axonal damage in MS (ID 902)

Speakers
Presentation Number
P0119
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

The level of neurofilament light chain (NfL), a major component of the neuronal cytoskeleton, in plasma or cerebrospinal fluid (CSF) is considered a promising biomarker in multiple sclerosis (MS) for inflammation-mediated axonal damage.

Objectives

The relation between NfL levels and MS specific neuropathological measures is not yet known, and is the subject of this study.

Methods

In this autopsy study (n=105), CSF NfL levels were measured using a Simoa assay and were correlated with hallmarks for acute and chronic damage axonal damage, clinical and pathological donor characteristics, and to proportions and activity of MS white matter lesions determined with myelin and HLA stainings.

Results

CSF NfL levels correlated with presence of acute axonal damage features (APP+ bulbs: p=0.04, APP+ axons: p=0.03) and correlated negatively with axonal density (Bielschowsky+ axons: p=8.3e-3) in the normal appearing pyramid tract. As CSF NfL levels were confounded by stroke (<1 year before death, p=2.0e-3), these donors were excluded from further MS specific clinical and neuropathological analysis. NfL correlated negatively with disease duration (p=6.9e-3), thus with more severe MS. NfL levels positively correlated with the proportion of active MS lesions containing foamy microglia (p=9.85e-10) and not those containing ramified microglia. NfL levels of donors without atrophy at neuropathological examination were positively correlated with the proportion of mixed lesions with foamy microglia (p=1.75e-3), and negatively correlated with the proportion of inactive lesions (p=5.66e-3) and remyelinated lesion presence (p=0.04).

Conclusions

We validated that CSF NfL levels reflect pathological hallmarks of acute disease activity and concomitant axonal degeneration. These observations support the clinical use of NfL to monitor these neuropathological processes in people with MS.

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