Comparison Of Human And Mouse Models Of Alzheimer’s Disease Based On Brain Transcriptomics

Background Alzheimer’sdisease（AD）is a neurodegenerative disease with insidious onset and progressive development,mainly occurring in the elderly population,and its prevalence increases significantly with age.The main manifestations of patients are reduced cognitive functions such as learning and memory.When using AD mouse model to develop targeted drugs for THE treatment of AD,the drugs applied to mice are often not significant or even have completely opposite effects for the treatment of Human AD.Objective: to study method of analysis by single-cell transcriptome and mice in the AD and the differences between the normal group,and the differences between cell types of the groups,and then by comparing the differences between the same cell type of mice and humans genetic characteristics,similarities and differences between the model of mice and humans,provide a reference for subsequent drug development and targeted therapy.PURPOSE By single-cell transcriptome study methods to analyze the differences between AD and normal groups of mice and humans,and the differences between cell types of the groups,and then by comparing the differences between the same cell type of mice and humans genetic characteristics,similarities and differences between the model of mice and humans,provide a reference for subsequent drug development and targeted therapyMETHOD Single nuclear sequencing data: Using gene expression database（gene expression omnibus https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi）,the sample data sets GSE157827 data set,sample is the prefrontal cortex,brain areas of the brain,Contains six samples,three samples（GSM4775661^GSM4775663）of patients with Alzheimer’s disease,and three samples of normal subjects.The data set of the mouse samples was GSE143758,which was the prefrontal cortex brain region of the mouse brain and contained four samples,including one 5x FAD and wild-type C57BL/6 of the 7-monthold mouse and one 5x FAD and wild-type C57BL/6 of the 10-month-old mouse.RESUILT 1.BSG,CST3,CLU,GJA1,APOE,MLC1,CD81,FTH1 and PTN were highly expressed in human astrocytes.Cst3 gene was up-regulated in astrocytes and oligodendrocytes of 7-month-old mice,but not significantly in 10-monthold mice.The expression levels of Clu and Gja1 genes were up-regulated in astrocytes of 7-month-old and 10-month-old mice 2.In human oligodendrocytes,APOD,ACTB,CD81 and FTH1 genes were highly expressed in human AD samples.APOD and FTH1 genes were highly expressed in oligodendrocytes of 10-month-old mice,and ACTB was highly expressed in astrocytes of 10-month-old mice.CONCLUSION In this study,single-cell transcriptomic analysis of prefrontal lobes in mouse and human brain tissues showed that the human AD cell response was significantly inconsistent with the 5x FAD mouse model of Aβ accumulation.