Dysregulated bioenergetics pathways in the Alzheimer’s mouse brain

Abstract

AbstractBackgroundAlzheimer’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.MethodRNA‐seq analysis was done to compare the transcriptome in the brain of 5XFAD mice to the WT brain.ResultThere was significant changes in the expression of genes related to pathways such as, oxidation‐reduction, oxidative phosphorylation, innate immune response, ribosomal protein synthesis, and ubiquitin proteosome system. The most striking feature was the alteration of the 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 “Gordian knot” 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 energeticsConclusionWe 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 compared to the WT.