Abstract
Alzheimer's disease (AD) is the most common cause for dementia in human. Currently, more than 46 million people in the world suffer from AD and it is estimated that by 2050 this number increases to more than 131 million. AD is considered as a complex disease. Therefore, understanding the mechanism of AD is a universal challenge. Nowadays, a huge number of disease-related high-throughput “omics” datasets are freely available. Such datasets contain valuable information about disease-related pathways and their corresponding gene interactions. In the present work, a three-way interaction model is used as a novel approach to understand AD-related mechanisms. This model can trace the dynamic nature of co-expression relationship between two genes by introducing their link to a third gene. Apparently, such relationships cannot be traced by the classical two-way interaction model. Liquid association method was applied to capture the statistically significant triplets which are involved in three-way interaction. Subsequently, gene set enrichment analysis (GSEA) and gene regulatory network (GRN) inference were applied to analyze the biological relevance of the statistically significant triplets. The results of this study suggest that the innate immunity processes are important in AD. Specifically, our results suggest that H2-Ob as the switching gene and the gene pair {Csf1r, Milr1} form a statistically significant and biologically relevant triplet, which may play an important role in AD. We propose that the homeostasis-related link between mast cells and microglia is presumably controlled with H2-Ob expression levels as a switching gene.
Highlights
Alzheimer’s disease (AD) is the most common cause for dementia in human
After preprocessing and normalization using robust multi-array analysis method, the final dataset consisted of 30 samples including 15 wild type and 15 APP/PS1 transgenic samples (It should be noted that two arrays (i.e., 15.w.3 and 26.w.12) were discarded from dataset due to low quality)
gene set enrichment analysis (GSEA) was performed with p-value
Summary
Alzheimer’s disease (AD) is the most common cause for dementia in human. AD often affects individuals over the age of 60, with increasing risk by age. Based on the last report of the AD International, more than 46 million people in the world suffer from AD and it is estimated that by 2050 this number increases to more than 131 million [1]. Switching mechanisms in Alzheimer’s disease complex progression of neurodegeneration that results in memory impairment and loss of other cognitive processes, as well as the presence of non-cognitive symptoms including delusions, agitation and changes in behavior and personality [2]. The causes of AD and its progress are not well known yet, it is characterized by the presence of amyloid plaques and neurofibrillary tangles outside and inside the neuronal cells, respectively. Reduction in neuronal synapses following the cellular death in hippocampus area of brain, can be the reason for loss of spatial memory and anomaly in patients’ behavior [3]
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