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

Zhi-Ping Liu,Yong Wang,Xiang-Sun Zhang,Luonan Chen

doi:10.1186/1752-0509-4-s2-s11

Abstract

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.

Highlights

Alzheimer’s disease (AD) is a major neurodegenerative disorder leading to amnesia, cognitive impairment and dementia in the elderly
We focus on the spatial pathway clusters in different AD brain regions and the crosstalks among pathways by integrating protein-protein interaction (PPI) and gene expression data
Clusters of AD related pathways We built a network of pathways by integrating the pathway information from Kyoto encyclopedia of genes and genomes (KEGG) [27] and the proteinprotein interaction network

Summary

Introduction

Alzheimer’s disease (AD) is a major neurodegenerative disorder leading to amnesia, cognitive impairment and dementia in the elderly. This type of lesions results from dysfunctional protein cooperations in the biological pathways. The availability and integration of high-throughput gene expression data [10] and the Biological processes in a cell are carried out through interactions among many proteins [11], which are functional units and generally achieve specific tasks cooperatively [2]. Genes with similar expression profiles are more likely to encode interacting proteins to coordinately achieve a particular function [11,12]. We aim to integrate the interrelated transcriptomic and interactomic information together to investigate AD related pathways

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