Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease, still incurable. The disease is highly heterogenous both genetically and phenotypically. Therefore, developing efficacious treatments is challenging in many aspects because it is difficult to predict the rate of disease progression and stratify the patients to minimize statistical variability in clinical studies. Moreover, there is a lack of sensitive measures of therapeutic effect to assess whether a pharmacological intervention ameliorates the disease. There is also urgency of markers that reflect a molecular mechanism dysregulated by ALS pathology and can be rescued when a treatment relieves the condition. Here, we summarize and discuss biomarkers tested in multicentered studies and across different laboratories like neurofilaments, the most used marker in ALS clinical studies, neuroinflammatory-related proteins, p75^ECD, p-Tau/t-Tau, and UCHL1. We also explore the applicability of muscle proteins and extracellular vesicles as potential biomarkers.

肌萎缩侧索硬化症 (ALS) 是最常见的运动神经元疾病，但仍无法治愈。该疾病在遗传和表型上都具有高度异质性。因此，开发有效的治疗方法在许多方面都具有挑战性，因为很难预测疾病进展的速度并对患者进行分层以尽量减少临床研究中的统计变异性。此外，缺乏敏感的治疗效果测量方法来评估药物干预是否能改善疾病。还迫切需要找到反映 ALS 病理失调的分子机制的标记物，并且当治疗缓解病情时可以挽救这些标记物。在这里，我们总结并讨论了在多中心研究和不同实验室中测试的生物标志物，例如神经丝（ALS 临床研究中最常用的标志物）、神经炎症相关蛋白、p75^ECD、p-Tau/t-Tau 和 UCHL1。我们还探索了肌肉蛋白和细胞外囊泡作为潜在生物标志物的适用性。