Translational Neurodegeneration Research and Neuropathology Lab, Department of Clinical Medicine (KlinMed), Medical Faculty, University of Oslo (UiO) and Section of Neuropathology Research, Department of Pathology, Clinics for Laboratory Medicine (KLM), Oslo University Hospital (OUS), Sognsvannsveien 20, Oslo NO-0372, Norway.
Proteomics Core Facility, Department of Immunology, Oslo University Hospital (OUS) and University of Oslo (UiO), Faculty of Medicine, Sognsvannsveien 20, Oslo NO-0372, Norway.
J Neurosci Methods. 2024 Nov;411:110239. doi: 10.1016/j.jneumeth.2024.110239. Epub 2024 Aug 3.
Mass spectrometry (MS)-based cerebrospinal fluid (CSF) proteomics is an important method for discovering biomarkers of neurodegenerative diseases. CSF serves as a reservoir for interstitial fluid (ISF), and extensive communication between the two fluid compartments helps to remove waste products from the brain.
We performed proteomic analyses of both CSF and ISF fluid compartments using intracerebral microdialysis to validate and detect novel biomarkers of Alzheimer's disease (AD) in APPtg and C57Bl/6J control mice.
We identified up to 625 proteins in ISF and 4483 proteins in CSF samples. By comparing the biofluid profiles of APPtg and C57Bl/6J mice, we detected 37 and 108 significantly up- and downregulated candidates, respectively. In ISF, 7 highly regulated proteins, such as Gfap, Aldh1l1, Gstm1, and Txn, have already been implicated in AD progression, whereas in CSF, 9 out of 14 highly regulated proteins, such as Apba2, Syt12, Pgs1 and Vsnl1, have also been validated to be involved in AD pathogenesis. In addition, we also detected new interesting regulated proteins related to the control of synapses and neurotransmission (Kcna2, Cacng3, and Clcn6) whose roles as AD biomarkers should be further investigated.
This newly established combined protocol provides better insight into the mutual communication between ISF and CSF as an analysis of tissue or CSF compartments alone.
The use of multiple fluid compartments, ISF and CSF, for the detection of their biological communication enables better detection of new promising AD biomarkers.
基于质谱（MS）的脑脊液（CSF）蛋白质组学是发现神经退行性疾病生物标志物的重要方法。CSF 是间质液（ISF）的储库，两者之间的广泛交流有助于从大脑中清除废物。
我们使用脑内微透析对 CSF 和 ISF 液室进行蛋白质组学分析，以验证和检测 APPtg 和 C57Bl/6J 对照小鼠阿尔茨海默病（AD）的新型生物标志物。
我们在 ISF 样本中鉴定出多达 625 种蛋白质，在 CSF 样本中鉴定出 4483 种蛋白质。通过比较 APPtg 和 C57Bl/6J 小鼠的生物流体图谱，我们分别检测到 37 种和 108 种显著上调和下调的候选物。在 ISF 中，7 种高度调节的蛋白质，如 Gfap、Aldh1l1、Gstm1 和 Txn，已经与 AD 进展有关，而在 CSF 中，14 种高度调节的蛋白质中有 9 种，如 Apba2、Syt12、Pgs1 和 Vsnl1，也已被证实与 AD 发病机制有关。此外，我们还检测到与控制突触和神经递质有关的新的有趣调节蛋白（Kcna2、Cacng3 和 Clcn6），它们作为 AD 生物标志物的作用应进一步研究。
新建立的联合方案提供了更好的洞察 ISF 和 CSF 之间的相互通讯，因为单独分析组织或 CSF 隔室。
使用多个液室，ISF 和 CSF，用于检测它们的生物学通讯，可以更好地检测新的有前途的 AD 生物标志物。
