Sprengel Jannik, Berezhnoy Georgy, Trautwein Christoph
Core Facility Metabolomics & Werner Siemens Imaging Center, Medical Faculty University of Tübingen, Tübingen, Germany.
Methods Mol Biol. 2025;2914:229-250. doi: 10.1007/978-1-0716-4462-1_17.
In the last decades, the prevalence of neurodegenerative disorders such as Parkinson's disease, dementia and stroke has significantly increased. The lack of early-stage biomarkers hereby is a major reason for poor outcomes and limited treatment options. Metabolism alterations are a major driver and readout of neurological implications; however, it can be assessed only to a very minor extent by non-invasive imaging technologies. By contrast, typical diagnostic biofluids like serum or urine reflect metabolic changes on the systemic scale and are not specific to the brain. That's why the analysis of cerebrospinal fluid (CSF) using metabolomic techniques offers a great perspective to better stratify patients with neurological implications. However, as metabolites can readily degrade and CSF collection in a clinical environment is challenging, several confounders have to be considered. Furthermore, no single technique can measure the full CSF metabolome. Hence in this work we used directly collected and quenched CSF for a multi-modal metabolomics profiling approach to define the ex vivo baseline of the human CSF metabolome by robust Nuclear Magnetic Resonance (NMR) spectroscopy and latest state of the art liquid chromatography (LC) ion mobility spectrometry mass spectrometry (IMS-MS).
在过去几十年中，帕金森病、痴呆症和中风等神经退行性疾病的患病率显著上升。缺乏早期生物标志物是导致预后不良和治疗选择有限的主要原因。代谢改变是神经病变的主要驱动因素和表现形式；然而，非侵入性成像技术只能在非常有限的程度上对其进行评估。相比之下，血清或尿液等典型诊断生物流体反映的是全身范围内的代谢变化，并非大脑所特有。这就是为什么使用代谢组学技术分析脑脊液（CSF）为更好地对有神经病变的患者进行分层提供了广阔前景。然而，由于代谢物容易降解，且在临床环境中收集脑脊液具有挑战性，因此必须考虑几个混杂因素。此外，没有单一技术能够测量完整的脑脊液代谢组。因此，在这项工作中，我们使用直接收集并淬灭的脑脊液进行多模态代谢组学分析，通过强大的核磁共振（NMR）光谱和最新的液相色谱（LC）离子淌度质谱（IMS-MS）来确定人类脑脊液代谢组的离体基线。
