对脑脊液进行定量蛋白质组学分析，以鉴定阿尔茨海默病的候选生物标志物。
Quantitative Proteomic Profiling of Cerebrospinal Fluid to Identify Candidate Biomarkers for Alzheimer's Disease.
机构信息
Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, 560029, India.
Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India.
出版信息
Proteomics Clin Appl. 2019 Jul;13(4):e1800105. doi: 10.1002/prca.201800105. Epub 2019 Jan 25.
PURPOSE
The aim of this study is to identify the potential cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease and to evaluate these markers on independent CSF samples using parallel reaction monitoring (PRM) assays.
EXPERIMENTAL DESIGN
High-Resolution mass spectrometry and tandem mass tag (TMT) multiplexing technology are employed to identify potential biomarkers for Alzheimer's disease. Some of the identified potential biomarkers are validated using PRM assays.
RESULTS
A total of 2327 proteins are identified in the CSF of which 139 are observed to be significantly altered in the CSF of AD patients. The proteins altered in AD includes a number of known AD marker such as MAPT, NPTX2, VGF, GFAP, and NCAM1 as well as novel biomarkers such as PKM and YWHAG. These findings are validated in a separate set of CSF specimens from AD dementia patients and controls. NPTX2, in combination with PKM or YWHAG, leads to the best results with AUCs of 0.935 and 0.933, respectively.
CONCLUSIONS AND CLINICAL RELEVANCE
The proteins that are found to be altered in the CSF of patients with AD could be used for monitoring disease progression and therapeutic response and perhaps also for early detection once they are validated in larger studies.
目的
本研究旨在确定阿尔茨海默病（AD）的潜在脑脊液（CSF）生物标志物，并使用平行反应监测（PRM）分析对独立的 CSF 样本进行评估。
实验设计
采用高分辨率质谱和串联质量标签（TMT）多重技术来鉴定 AD 的潜在生物标志物。使用 PRM 分析对部分鉴定出的潜在生物标志物进行验证。
结果
共鉴定出 CSF 中的 2327 种蛋白质，其中 139 种在 AD 患者的 CSF 中明显改变。AD 中改变的蛋白质包括许多已知的 AD 标志物，如 MAPT、NPTX2、VGF、GFAP 和 NCAM1，以及新的生物标志物，如 PKM 和 YWHAG。这些发现在另一组来自 AD 痴呆患者和对照者的 CSF 标本中得到了验证。NPTX2 与 PKM 或 YWHAG 联合使用，可分别获得 AUC 为 0.935 和 0.933 的最佳结果。
结论和临床相关性
在 AD 患者 CSF 中发现改变的蛋白质可用于监测疾病进展和治疗反应，在更大规模的研究中得到验证后，也许还可用于早期检测。
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