Differential network analyses of Alzheimer's disease identify early events in Alzheimer's disease pathology.
Differential network analyses of Alzheimer's disease identify early events in Alzheimer's disease pathology.
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DOI：
10.1155/2014/721453
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发表时间：
2014
影响因子：
--
通讯作者：
Ray M
中科院分区：
文献类型：
--
作者：
Xia J;Rocke DM;Perry G;Ray M
在晚发性阿尔茨海默病（AD）中，多个大脑区域不会同时受到影响。比较受影响区域的基因表达，以确定生物过程中的差异扰动，可以导致更深入地了解AD的发病机制和早期特征。我们从四个受AD影响的大脑区域的单细胞微阵列数据中鉴定了差异表达（DE）基因：内嗅皮质（EC）、海马（HIP）、后扣带回皮质（PCC）和颞中回（MTG）。我们将DE基因在四个脑区组织成区域特异性基因共表达网络。在共表达网络中进行差分邻域分析，以识别其直接邻居具有低拓扑重叠（TO）的基因。低TO基因用于表征两个区域之间的生物学差异。我们的分析表明，氧化应激增加，沿着神经元脂质代谢的改变，可能是AD病理学中发生的一些非常早期的事件。细胞防御机制试图干预，但失败了，最终导致AD病理随着疾病的进展。此外，在两个独立的蛋白质相互作用网络中的低TO基因的疾病注释已经导致癌症、糖尿病、肾脏疾病和心血管疾病之间的关联。
In late-onset Alzheimer's disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with low topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.