We aimed to investigate neuronal and astroglial markers in multiple sclerosis (MS) and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders (NMOSD) patients and compare their clinical implications according to age groups.

Serum levels of synaptic proteins may change with age and related neurodegeneration, affecting their clinical implication as a disease biomarker. 

With 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). We assessed correlations of these markers with age and those with Expanded Disability Status Scale (EDSS). Additionally, we evaluated correlations between serum markers and EDSS according to three age groups (≤44, 45-54, ≥55 years).

GFAP levels significantly increased with age in both diseases, while NfL levels showed significant positive correlations with age in NMOSD only. Both markers revealed significant positive correlations with EDSS in both diseases. In MS patients, the degrees of correlations between serum markers and EDSS were similar across the age groups. Meanwhile, in NMOSD patients, positive GFAP–EDSS correlations were distinctively stronger in the youngest group than in the oldest group. Conversely, positive NfL–EDSS correlations in NMOSD were not demonstrated in the youngest group, whereas prominently significant in the oldest group.

In MS/NMOSD, serum NfL and GFAP levels may both reflect disease severity. However, the degree to which these markers reflect disease severity differ significantly with patient age in NMOSD, but not in MS, suggesting that different strategies may be necessary to interpret biomarker results according to age and disease type.