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Identifying dysfunctional crosstalk of pathways in various regions of Alzheimer's disease brains

机译:识别阿尔茨海默氏病大脑各个区域中通路的功能障碍

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BackgroundAlzheimer's disease (AD) is a major neurodegenerative disorder leading to amnesia, cognitive impairment and dementia in the elderly. Usually this type of lesions results from dysfunctional protein cooperations in the biological pathways. In addition, AD progression is known to occur in different brain regions with particular features. Thus identification and analysis of crosstalk among dysregulated pathways as well as identification of their clusters in various diseased brain regions are expected to provide deep insights into the pathogenetic mechanism.ResultsHere we propose a network-based systems biology approach to detect the crosstalks among AD related pathways, as well as their dysfunctions in the six brain regions of AD patients. Through constructing a network of pathways, the relationships among AD pathway and its neighbor pathways are systematically investigated and visually presented by their intersections. We found that the significance degree of pathways related to the fatal disorders and the pathway overlapping strength can indicate the impacts of these neighbored pathways to AD development. Furthermore, the crosstalks among pathways reveal some evidence that the neighbor pathways of AD pathway closely cooperate and play important tasks in the AD progression.ConclusionsOur study identifies the common and distinct features of the dysfunctional crosstalk of pathways in various AD brain regions. The global pathway crosstalk network and the clusters of relevant pathways of AD provide evidence of cooperativity among pathways for potential pathogenesis of the neuron complex disease.
机译:背景阿尔茨海默氏病(AD)是导致老年人失忆,认知障碍和痴呆的主要神经退行性疾病。通常,这种类型的病变是由于生物学途径中功能失调的蛋白质合作所致。另外,已知AD进展发生在具有特定特征的不同大脑区域中。因此,对失调的通路之间的串扰进行鉴定和分析,以及在各种患病的大脑区域中对它们的簇进行鉴定,有望对致病机理提供深入的了解。结果在此,我们提出了一种基于网络的系统生物学方法来检测AD相关通路之间的串扰。以及它们在AD患者的六个大脑区域的功能障碍。通过构建路径网络,系统地研究了AD路径与其相邻路径之间的关系,并通过它们的交叉点直观地呈现了它们。我们发现与致命性疾病相关的途径的显着程度和途径重叠强度可以表明这些邻近途径对AD发育的影响。此外,这些通路之间的串扰揭示了一些证据,表明AD通路的相邻通路紧密协作并在AD进展中起着重要的作用。结论我们的研究确定了各个AD脑区域中通路失调串扰的共同和独特特征。全局通路串扰网络和AD相关通路的簇为神经元复杂疾病的潜在发病机理提供了通路之间协同性的证据。

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