Ray Monika, Zhang Weixiong
Washington University School of Engineering, Dept of Computer Science and Engineering, Saint Louis, MO 63130, USA.
BMC Syst Biol. 2010 Oct 6;4:136. doi: 10.1186/1752-0509-4-136.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder involving variations in the transcriptome of many genes. AD does not affect all brain regions simultaneously. Identifying the differences among the affected regions may shed more light onto the disease progression. We developed a novel method involving the differential topology of gene coexpression networks to understand the association among affected regions and disease severity.
We analysed microarray data of four regions--entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC) and middle temporal gyrus (MTG) from AD affected and normal subjects. A coexpression network was built for each region and the topological overlap between them was examined. Genes with zero topological overlap between two region-specific networks were used to characterise the differences between the two regions.
Results indicate that MTG shows early AD pathology compared to the other regions. We postulate that if the MTG gets affected later in the disease, post-mortem analyses of individuals with end-stage AD will show signs of early AD in the MTG, while the EC, HIP and PCC will have severe pathology. Such knowledge is useful for data collection in clinical studies where sample selection is a limiting factor as well as highlighting the underlying biology of disease progression.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，涉及许多基因转录组的变化。AD不会同时影响所有脑区。识别受影响区域之间的差异可能会为疾病进展提供更多线索。我们开发了一种涉及基因共表达网络差异拓扑的新方法，以了解受影响区域与疾病严重程度之间的关联。
我们分析了来自AD患者和正常受试者的四个区域——内嗅皮质（EC）、海马体（HIP）、后扣带回皮质（PCC）和颞中回（MTG）的微阵列数据。为每个区域构建了一个共表达网络，并检查了它们之间的拓扑重叠。两个区域特异性网络之间拓扑重叠为零的基因用于表征两个区域之间的差异。
结果表明，与其他区域相比，MTG表现出早期AD病理特征。我们推测，如果MTG在疾病后期受到影响，晚期AD患者的尸检分析将显示MTG中有早期AD迹象，而EC、HIP和PCC将出现严重病理变化。这些知识对于临床研究中的数据收集很有用，在临床研究中样本选择是一个限制因素，同时也突出了疾病进展的潜在生物学机制。
