This article is part of the supplement: Selected articles from the Third International Symposium on Optimization and Systems Biology
Identifying dysfunctional crosstalk of pathways in various regions of Alzheimer's disease brains
1 Key Laboratory of Systems Biology and SIBS-Novo Nordisk Translational Research Centre for PreDiabetes, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2 Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China
3 Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan
BMC Systems Biology 2010, 4(Suppl 2):S11 doi:10.1186/1752-0509-4-S2-S11Published: 13 September 2010
Alzheimer'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.
Here 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.
Our 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.