Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Department of Medicine, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, South Korea.
Ann Clin Transl Neurol. 2020 Jun;7(6):992-1001. doi: 10.1002/acn3.51070. Epub 2020 Jun 4.
Serum 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.
Using 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).
Although 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.
The 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.
血清突触蛋白水平可能会随年龄相关的神经退行性变而改变，从而影响其作为疾病生物标志物的临床意义。我们旨在研究多发性硬化症（MS）和水通道蛋白 4 抗体阳性视神经脊髓炎谱系疾病（NMOSD）患者的神经元和星形胶质细胞标志物，以比较根据年龄这些标志物的临床意义。
使用单分子阵列测定法，我们测量了连续 MS（n=117）和 NMOSD（n=63）患者血清中的神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）。对于每种疾病，我们根据三个年龄组（≤44、45-54 和≥55 岁）评估了这些标志物与疾病严重程度（扩展残疾状况量表 [EDSS]）评分之间的相关性。
尽管 NMOSD 患者的血清 GFAP 水平明显高于 MS 患者，但两种血清标志物的水平与两种疾病的 EDSS 评分均呈显著正相关。在 MS 患者中，血清 NfL（或 GFAP）水平与 EDSS 评分之间的相关性程度在所有年龄组中均相似。然而，在 NMOSD 患者中，GFAP-EDSS 相关性在最年轻组中明显强于最年长组。相反，在最年轻的 NMOSD 患者中，没有阳性的 NfL-EDSS 相关性，但在最年长的组中则有。
在 NMOSD 中，血清 NfL 和 GFAP 水平反映疾病严重程度的程度与患者年龄有很大差异，但在 MS 中则没有。这些发现表明疾病之间的病理过程和进展不同；因此，根据患者年龄和疾病类型，血清生物标志物水平可能需要以不同的方式进行解释。
