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Molecular Network Analysis of the Urinary Proteome of Alzheimer’s Disease Patients

机译：阿尔茨海默氏病患者尿蛋白的分子网络分析

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Background/Aims: The identification of predictive biomarkers for Alzheimer’s disease (AD) from urine would aid in screening for the disease, but information about biological and pathophysiological changes in the urine of AD patients is limited. This study aimed to explore the comprehensive profile and molecular network relations of urinary proteins in AD patients. Methods: Urine samples collected from 18 AD patients and 18 age- and sex-matched cognitively normal controls were analyzed by mass spectrometry and semiquantified with the normalized spectral index method. Bioinformatics analyses were performed on proteins which significantly increased by more than 2-fold or decreased by less than 0.5-fold compared to the control (p 0.05) using DAVID bioinformatics resources and KeyMolnet software. Results: The levels of 109 proteins significantly differed between AD patients and controls. Among these, annotation clusters related to lysosomes, complement activation, and gluconeogenesis were significantly enriched. The molecular relation networks derived from these proteins were mainly associated with pathways of lipoprotein metabolism, heat shock protein 90 signaling, matrix metalloproteinase signaling, and redox regulation by thioredoxin. Conclusion: Our findings suggest that changes in the urinary proteome of AD patients reflect systemic changes related to AD pathophysiology.
机译：背景/目的：从尿液中识别出阿尔茨海默氏病（AD）的预测性生物标志物有助于筛查该疾病，但有关AD患者尿液中生物学和病理生理变化的信息有限。本研究旨在探讨AD患者尿蛋白的全面概况和分子网络关系。方法：通过质谱分析从18位AD患者和18位年龄和性别匹配的认知正常对照中收集的尿液样品，并使用归一化光谱指数法进行半定量。使用DAVID生物信息学资源和KeyMolnet软件，对与对照相比显着增加2倍以上或减少少于0.5倍的蛋白质进行了生物信息学分析（p <0.05）。结果：AD患者和对照组之间的109种蛋白质水平显着不同。其中，与溶酶体，补体激活和糖异生有关的注释簇显着丰富。从这些蛋白质衍生的分子关系网络主要与脂蛋白代谢，热休克蛋白90信号传导，基质金属蛋白酶信号传导和硫氧还蛋白调节氧化还原有关。结论：我们的发现表明，AD患者尿蛋白质组的变化反映了与AD病理生理相关的系统性变化。

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