Laboratoire de Biochimie et Biologie Moléculaire, CHRU Bretonneau, 2 Boulevard Tonnellé, 37000 Tours, France.
UMR 1253 iBrain, Université de Tours, Inserm, 10 Boulevard Tonnellé, 37000 Tours, France.
Int J Mol Sci. 2023 Jul 7;24(13):11196. doi: 10.3390/ijms241311196.
Central nervous system (CNS) barrier impairment has been reported in amyotrophic lateral sclerosis (ALS), highlighting its potential significance in the disease. In this context, we aim to shed light on its involvement in the disease, by determining albumin quotient (QAlb) at the time of diagnosis of ALS in a large cohort of patients. Patients from the university hospital of Tours ( = 307) were included in this monocentric, retrospective study. In total, 92 patients (30%) had elevated QAlb levels. This percentage was higher in males (43%) than in females (15%). Interestingly, QAlb was not associated with age of onset, age at sampling or diagnostic delay. However, we found an association with ALS functional rating scale-revised (ALSFRS-r) at diagnosis but this was significant only in males. The QAlb levels were not linked to the presence of a pathogenic mutation. Finally, we performed a multivariate survival analysis and found that QAlb was significantly associated with survival in male patients (HR = 2.3, 95% CI = 1.2-4.3, = 0.009). A longitudinal evaluation of markers of barrier impairment, in combination with inflammatory biomarkers, could give insight into the involvement of CNS barrier impairment in the pathogenesis of the disease. The gender difference might guide the development of new drugs and help personalise the treatment of ALS.
中枢神经系统（CNS）屏障损伤已在肌萎缩侧索硬化症（ALS）中报道，强调了其在疾病中的潜在意义。在这种情况下，我们旨在通过在大量患者中确定 ALS 诊断时的白蛋白商（QAlb）来阐明其在疾病中的作用。我们的研究纳入了图尔大学医院的患者（n=307）。共有 92 名患者（30%）的 QAlb 水平升高。男性（43%）的这一比例高于女性（15%）。有趣的是，QAlb 与发病年龄、采样年龄或诊断延迟无关。然而，我们发现 QAlb 与诊断时的肌萎缩侧索硬化功能评定量表修订版（ALSFRS-r）有关，但仅在男性中具有统计学意义。QAlb 水平与致病性突变的存在无关。最后，我们进行了多变量生存分析，发现 QAlb 与男性患者的生存显著相关（HR=2.3，95%CI=1.2-4.3，p=0.009）。对屏障损伤标志物的纵向评估，结合炎症生物标志物，可能有助于深入了解 CNS 屏障损伤在疾病发病机制中的作用。性别差异可能为开发新的药物提供指导，并有助于 ALS 的个体化治疗。
