TREM2 Alteration Increases AD Biomarkers and is Associated with Key Genes with 5xFAD Mice Model Analysis on MODEL-AD Database

Abstract

AbstractAlzheimer Disease is a multifactorial disorder characterized by cognitive decline and memory loss. A key gene associated with AD is the TREM2 gene which has been identified as a risk factor for AD. Studies show that TREM2 functions in microglia regulation that controls the amount of AB proteins by the mechanisms of clearance and degradation. However, the exact mechanism of how the TREM2 variations like TREM2 KO and TREM2 R47H contribute to the progression of Alzheimer is still debated. Moreover, research into the levels of gene expression and measurements of biomarkers that contribute to progression of AD is very limited. In this paper, we conduct a comprehensive analysis of the biomarker concentration and gene regulatory behavior in TREM2 KO and TREM2 R47H mutated mice models from the MODEL AD database in order to gain understanding of how these variations contribute to the formation of biomarkers and contribute to AD progression.Our research indicates a correlation between the mutated mice model and the different biomarker concentrations in the brain like insoluble AB40 and 42 proteins, soluble AB40 and 42 proteins, and NFL, which shows that TREM2 gene may be associated with multiple biomarkers. Moreover, we identified some key genes that were associated with the downregulation of the TREM2 gene with the TREM2 KO mice model gene analysis. Finally, we took the confocal images of the TREM2 KO mice model to analyze the effect that the lack of TREM2 extracellular receptor has on the neuritic dystrophy in the brain. Overall, we analyzed the biomarker concentration, gene regulatory activity, and the neuritic effects of the TREM2 KO and TREM2 R47H mutated variants of the TREM2 gene.