Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
METHODS: 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.
CONCLUSIONS: The use of multiple fluid compartments, ISF and CSF, for the detection of their biological communication enables better detection of new promising AD biomarkers.
METHODS: 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.
RESULTS: 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.
METHODS: 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.
CONCLUSIONS: The use of multiple fluid compartments, ISF and CSF, for the detection of their biological communication enables better detection of new promising AD biomarkers.
摘要：
背景：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用作间质液（ISF）的储存器，两个流体隔室之间的广泛交流有助于从大脑中清除废物。
方法：我们使用脑内微透析对CSF和ISF液隔室进行了蛋白质组学分析，以验证和检测APPtg和C57Bl/6J对照小鼠中阿尔茨海默病（AD）的新型生物标志物。
结果：我们在ISF中鉴定了多达625种蛋白质，在CSF样品中鉴定了4,483种蛋白质。通过比较APPtg和C57Bl/6J小鼠的生物流体谱，我们检测到37和108个显著上调和下调的候选人，分别。在ISF，7种高度调节的蛋白质，比如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，Apba2、Syt12、Pgs1和Vsnl1等也被证实参与AD的发病机制。此外,我们还检测到与突触控制和神经传递相关的新的有趣的调节蛋白(Kcna2,Cacng3和Clcn6),它们作为AD生物标志物的作用有待进一步研究.
方法：这种新建立的组合方案提供了对ISF和CSF之间相互交流的更好见解，作为对组织或CSF区室的单独分析。
结论：使用多个流体隔室，ISF和CSF，用于检测它们的生物通讯能够更好地检测新的有前途的AD生物标志物。
方法：我们使用脑内微透析对CSF和ISF液隔室进行了蛋白质组学分析，以验证和检测APPtg和C57Bl/6J对照小鼠中阿尔茨海默病（AD）的新型生物标志物。
结果：我们在ISF中鉴定了多达625种蛋白质，在CSF样品中鉴定了4,483种蛋白质。通过比较APPtg和C57Bl/6J小鼠的生物流体谱，我们检测到37和108个显著上调和下调的候选人，分别。在ISF，7种高度调节的蛋白质，比如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，Apba2、Syt12、Pgs1和Vsnl1等也被证实参与AD的发病机制。此外,我们还检测到与突触控制和神经传递相关的新的有趣的调节蛋白(Kcna2,Cacng3和Clcn6),它们作为AD生物标志物的作用有待进一步研究.
方法：这种新建立的组合方案提供了对ISF和CSF之间相互交流的更好见解，作为对组织或CSF区室的单独分析。
结论：使用多个流体隔室，ISF和CSF，用于检测它们的生物通讯能够更好地检测新的有前途的AD生物标志物。
