Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder and the most common form of motor neurone disease (MND) which is characterized by the damage and death of motor neurons in the brain and spinal cord of affected individuals. Due to the heterogeneity of the disease, a better understanding of the interaction between genetics and biochemistry with the identification of biomarkers is crucial for therapy development. In this study, we used cerebrospinal fluid (CSF) RNA-sequencing data from the New York Genome Center (NYGC) ALS Consortium and analyzed differential gene expression between 47 MND individuals and 29 healthy controls. Pathway analysis showed that the affected genes are enriched in many pathways associated with ALS, including nucleocytoplasmic transport, autophagy, and apoptosis. Moreover, we assessed differential expression on both gene- and transcript-based levels and demonstrate that the expression of previously identified potential biomarkers, including CAPG, CCL3, and MAP2, was significantly higher in MND individuals. Ultimately, this study highlights the transcriptomic composition of CSF which enables insights into changes in the brain in ALS and therefore increases the confidence in the use of CSF for biomarker development.

中文翻译：

---

脑脊液转录组分析可识别 MND 个体中 ALS 通路的富集和 RNA 生物标志物。

肌萎缩侧索硬化症 (ALS) 是一种致命的神经退行性疾病，也是运动神经元疾病 (MND) 的最常见形式，其特征是受影响个体的大脑和脊髓中的运动神经元受损和死亡。由于疾病的异质性，更好地了解遗传学和生物化学之间的相互作用以及生物标志物的识别对于治疗开发至关重要。在这项研究中，我们使用来自纽约基因组中心 (NYGC) ALS 联盟的脑脊液 (CSF) RNA 测序数据，分析了 47 名 MND 个体和 29 名健康对照之间的差异基因表达。通路分析表明，受影响的基因在与 ALS 相关的许多通路中富集，包括核质转运、自噬和细胞凋亡。此外，我们评估了基因和转录水平上的差异表达，并证明先前确定的潜在生物标志物（包括 CAPG、CCL3 和 MAP2）的表达在 MND 个体中显着较高。最终，这项研究强调了 CSF 的转录组组成，这使得我们能够深入了解 ALS 中大脑的变化，从而增加了使用 CSF 进行生物标志物开发的信心。