Transcriptional dysregulation study reveals a core network involving the genesis for Alzheimer’s disease

Meng, G.; Mei, H.

doi:10.1101/240002

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bioRxiv · 10.1101/240002

Transcriptional dysregulation study reveals a core network involving the genesis for Alzheimer’s disease

Meng, G.·Mei, H.

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Abstract

BackgroundThe pathogenesis of Alzheimers disease is associated with dysregulation at different levels from transcriptome to cellular functioning. Such complexity necessitates investigations of disease etiology to be carried out considering multiple aspects of the disease and the use of independent strategies. The established works more emphasized on the structural organization of gene regulatory network while neglecting the internal regulation changes.\n\nMethodsApplying a strategy different from popularly used co-expression network analysis, this study investigated the transcriptional dysregulations during the transition from normal to disease states.\n\nResults97 genes were predicted as dysregulated genes, which were also associated with clinical outcomes of Alzheimers disease. Both the co-expression and differential co-expression analysis suggested these genes to be interconnected as a core network and that their regulations were strengthened during the transition to disease states. Functional studies suggested the dysregulated genes to be associated with aging and synaptic function. Further, we checked the evolutionary conservation of the gene co-expression and found that human and mouse brain might have divergent transcriptional co-regulation even when they had conserved gene expression profiles.\n\nConclusionOverall, our study reveals a profile of transcriptional dysregulation in the genesis of Alzheimers disease by forming a core network with altered regulation; the core network is associated with Alzheimers diseases by affecting the aging and synaptic functions related genes; the gene regulation in brain may not be conservative between human and mouse.

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Meng, G., Mei, H.. 2017-12-26. Transcriptional dysregulation study reveals a core network involving the genesis for Alzheimer’s disease. https://doi.org/10.1101/240002

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