CELLS-ALBA, Carrer de la Llum 2-26, Cerdanyola del Valles, 08290 Barcelona, Spain.
Department of Neurology, University Medicine Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Cells. 2023 May 23;12(11):1451. doi: 10.3390/cells12111451.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, with the most common adult-onset neurodegenerative disorder affecting motoneurons. Although disruptions in macromolecular conformation and homeostasis have been described in association with ALS, the underlying pathological mechanisms are still not completely understood, and unambiguous biomarkers are lacking. Fourier Transform Infrared Spectroscopy (FTIR) of cerebrospinal fluid (CSF) is appealing to extensive interest due to its potential to resolve biomolecular conformation and content, as this approach offers a non-invasive, label-free identification of specific biologically relevant molecules in a few microliters of CSF sample. Here, we analyzed the CSF of 33 ALS patients compared to 32 matched controls using FTIR spectroscopy and multivariate analysis and demonstrated major differences in the molecular contents. A significant change in the conformation and concentration of RNA is demonstrated. Moreover, significantly increased glutamate and carbohydrates are found in ALS. Moreover, key markers of lipid metabolism are strongly altered; specifically, we find a decrease in unsaturated lipids and an increase in peroxidation of lipids in ALS, whereas the total amount of lipids compared to proteins is reduced. Our study demonstrates that FTIR characterization of CSF could represent a powerful tool for ALS diagnosis and reveals central features of ALS pathophysiology.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，最常见的成年发病的神经退行性疾病影响运动神经元。尽管与 ALS 相关的大分子构象和动态平衡的破坏已经被描述，但潜在的病理机制仍不完全清楚，并且缺乏明确的生物标志物。由于傅里叶变换红外光谱（FTIR）具有解析生物分子构象和含量的潜力，因此对脑脊液（CSF）的研究引起了广泛的兴趣，因为这种方法提供了一种非侵入性的、无标记的方法，可以在几微升 CSF 样本中识别特定的与生物学相关的分子。在这里，我们使用 FTIR 光谱和多元分析分析了 33 名 ALS 患者和 32 名匹配对照者的 CSF，并证明了分子含量的主要差异。证明了 RNA 的构象和浓度发生了显著变化。此外，在 ALS 中发现谷氨酸和碳水化合物显著增加。此外，脂质代谢的关键标志物也发生了强烈改变；具体而言，我们发现 ALS 中不饱和脂质减少，脂质过氧化增加，而与蛋白质相比，脂质总量减少。我们的研究表明，CSF 的 FTIR 特征可能代表 ALS 诊断的有力工具，并揭示了 ALS 病理生理学的核心特征。
