Abstract

ObjectivesSerum synaptic proteins levels may change with age‐related neurodegeneration, affecting their clinical implications as a disease biomarker. We aimed to investigate neuronal and astroglial markers in patients with multiple sclerosis (MS) and aquaporin‐4 antibody‐seropositive neuromyelitis optica spectrum disorders (NMOSD) to compare the clinical implications of these markers according to age.MethodsUsing single‐molecule array assays, we measured neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in sera from consecutive patients with MS (n = 117) and NMOSD (n = 63). For each disease, we assessed correlations between these markers and disease severity (Expanded Disability Status Scale [EDSS]) scores according to three age groups (≤44, 45–54, and ≥55 years).ResultsAlthough serum GFAP levels were significantly higher in patients with NMOSD than those with MS, levels of both serum markers revealed significant positive correlations with EDSS scores in both diseases. In MS patients, the degrees of correlation between serum NfL (or GFAP) levels and EDSS scores were similar across all age groups. However, in NMOSD patients, positive GFAP‐EDSS correlations were distinctively stronger in the youngest than in the oldest group. Conversely, there were no positive NfL‐EDSS correlations in NMOSD in the youngest group, but there were significant in the oldest group.InterpretationThe degrees to which serum NfL and GFAP levels reflect disease severity vary significantly with patient age in NMOSD, but not in MS. These findings suggest that the pathological processes and progression differ between the diseases; hence, serum biomarker levels may need to be interpreted differently according to patient age and disease type.

Highlights

  • Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are chronic inflammatory demyelinating diseases of the central nervous system.[1]

  • Serum neurofilament light protein (NfL) and glial fibrillary acidic protein (GFAP) levels were higher in NMOSD patients than MS patients; after adjusting for important clinical variables that may affect biomarker levels, only GFAP levels remained significantly elevated in NMOSD patients

  • We found that serum GFAP levels increased with age in patients with either MS or NMOSD, while serum NfL levels showed significant positive correlations with age in NMOSD only

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Summary

Introduction

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are chronic inflammatory demyelinating diseases of the central nervous system.[1] These disorders are characterized by relapses and deterioration, which necessitates biomarkers for long-term disease monitoring.[2] With the recent development of ultrasensitive single-molecule array (Simoa) technology,[3] serum neurofilament light protein (NfL), a neuronal damage marker, and glial fibrillary acidic protein (GFAP), an astrocyte-damage marker, have been suggested as a good biomarker candidate with high sensitivity.[4,5,6,7,8,9,10] processes associated with aging, such as neurodegeneration and related astrogliosis may influence these protein biomarkers;[6,11,12,13,14] these proteins’ clinical implications may differ depending on patient age. A progressive phase is rare in NMOSD and neurodegeneration in this disorder depends mainly on inflammatory relapses.[1]

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