Alteration of Cognitive Function in Aging and Alzheimer’s Disease Mice Is Related to Dysfunction of the Neuroimmune System

Abstract

Background: Both Alzheimer’s disease (AD) and aging have aging-related cognitive dysfunction with a high incidence. These neurological diseases cause serious cognitive problems in patients’ daily life. But the cognitive dysfunction mechanism in-depth of aging is far less known than that of AD. Objective: To reveal the different mechanisms of AD and aging-related cognitive dysfunction, we compared the mechanisms of aging and AD through analysis of differentially expressed genes. Methods: Mice were divided into four groups (3-month C57BL, 16-month C57BL, 3-month 3xTg AD mice, and 16-month 3xTg AD mice) according to genotype and age. The Morris water maze was employed to investigate the spatial cognition of mice. Differential expressions of genes of AD and aging were analyzed through RNA sequencing and GO, KEGG, Reactome analysis, and the dynamic change trend analysis. Microglia was stained with immunofluorescence and its numbers were counted for analysis. Results: The cognitive function of elderly mice were worse through testing with the Morris water maze. The cognitive function of 16-month 3xTg AD mice were worse than 16-month C57BL mice. The alteration tendencies of DE genes were uncovered, and microglia numbers increased during aging and AD progression through immunofluorescence. Conclusion: These results suggest that immune-related pathways might play a critical role in aging and AD-related cognitive dysfunction. Our research will help to provide some new potential targets for treating cognitive dysfunction in aging and AD.