Interactions of Cellular Energetic Gene Clusters in the Alzheimer’s Mouse Brain

Alzheimer’s disease (AD) is the most common cause of dementia in the aging population. The pathological characteristics include extracellular senile plaques and intracellular neurofibrillary tangles. In addition, mitochondrial dysfunction, oxidative stress, and neuroinflammation contribute to AD pathogenesis. In this study, we sought to determine the crosstalk between different pathways in the brain of 5XFAD mice, a mouse model for amyloid pathology, by RNA-seq analysis. We observed significant changes in the expression of genes (1288 genes; adj p value < 0.05; log2-fold > 1 and < 1) related to pathways including oxidation–reduction, oxidative phosphorylation, innate immune response, ribosomal protein synthesis, and ubiquitin proteosome system. The most striking feature was the downregulation of genes related to oxidation–reduction process with changes in the expression of a large number of mitochondrial genes. We also observed an upregulation of several immune response genes. Gene interaction network of oxidation–reduction related genes further confirmed a tight cluster of mitochondrial genes. Furthermore, gene interaction analysis of all the 1288 genes showed at least three distinct interaction clusters, with the predominant one relating to cellular energetics. In summary, we identified 1288 genes distinctly different in the 5XFAD brain compared to the WT brain and found cellular energetics to be the most distinct gene cluster in the AD mouse brain.