Abstract
Background: The pathogenesis of Alzheimer's 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.Methods: Applying a strategy different from popularly used co-expression network analysis, this study investigated the transcriptional dysregulations during the transition from normal to disease states.Results: Ninety- seven genes were predicted as dysregulated genes, which were also associated with clinical outcomes of Alzheimer's 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 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.Conclusion: Overall, our study reveals a core network of transcriptional dysregulation associated with the progression of Alzheimer's disease by affecting the aging and synaptic functions related genes; the gene regulation is not conserved in the human and mouse brains.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder most prevalent in people over the age of 65 years (Lashuel et al, 2002; Goedert and Spillantini, 2006; Prince et al, 2013)
We studied the transcriptional dysregulation by evaluating all the gene pair combinations for their co-expression changes, which can be referred as differential co-expression (DCE) analysis
To find the dysregulation associated with AD, we evaluated the co-expression changes in the brain of AD patients, which indicated the transcription regulation changes
Summary
The pathogenesis of Alzheimer’s disease is associated with dysregulation at different levels from transcriptome to cellular functioning. The established works more emphasized on the structural organization of gene regulatory network while neglecting the internal regulation changes
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