Underlying Genetic Links Between Alzheimer’s Disease And Vascular Dementia

Background and PurposeWith the aging of the global population,the incidence of dementia is increasing by years.Dementia seriously affect the quality of life of patients,and propose a huge burden to the patients themselves and their families and even the society as well.Therefore,dementia has become a hot research focus in domestic field and abroad.Alzheimer’s disease and vascular dementia are the two most common types of dementia.The symptoms of AD and VaD are similar and sometimes difficult to distinguish.In order to investigate the potential mechanism difference between the two diseases,we analyzed the differentially expressed genes between them。Next-generation sequencing,or high-throughput sequencing,has developed rapidly over the past decade.It is a method of sequencing millions of DNA fragments(or complementary DNA)at the same time.Compared with traditional methods,it can analyze multiple genes or gene regions simultaneously by single test,so it is applied quickly in clinical trials.in many clinical laboratories,next-generation sequencing is a detection method for germline and somatic gene mutations.detection of genetic diseases,familial diseases may include target plates,whole exons,whole genome or mitochondrial DNA sequencing.At present,many laboratories have used NGS techniques to detect hereditary diseases and tumor mutations.And with the development of technology,bioinformatics and various resources,NGS will be used more and more in clinic.MethodsTo investigate potential mechanistic differences between the two diseases,we analyzed differentially expressed genes between them and performed weighted gene coexpression network analysis(WGCNA)and other bioinformatics analyses.our results identify core pathways associated with AD and vascular dementia.during the WGCNA,different modules were developed according to the expression differences of the two diseases,including the enrichment analysis of module genes and the construction of protein-protein interaction networks to explore the core pathways related to them.The emerging diagnostic model or tools of AD and vascular dementia can be further verified in the gene expression profile of patients,which can not only reflect the serological response of dementia patients but can also indirectly predict the pathological changes of brain tissue.ResultsBased on the gene expression profiles obtained from databases and clinical samples,A total of 18019 co-expressed genes were shown.These co-expressed genes were analyzed and differentially expressed genes were obtained.Adoption of the WGCNA,of implementation four modules most relevant to the identification AD were obtained.two of these modules were found to be involved in KEGG pathways related to c AMP signaling pathway,neurotrophin signaling pathway,Gn RH signaling pathway,and ECM receptor interaction through functional enrichment analysis.Using co-expression genes of hub genes and KEGG pathways for further exploration,A total of 21 hub genes were obtained which might distinguish between AD and VAD.patients.Conclusions1、Analysis of expression profiles of brain tissue samples and blood profiles of9 patients and 3 healthy donors in GSE database,can indirectly reflect changes in brain-like transcriptome expression in the blood after dementia.2、By means of weighted gene coexpression network analysis(WGCNA),to further identify the impact of different modules on AD and VaD,exploring potential regulatory mechanisms.3、By WGCNA analysis,We built up modules related to AD and VAD,Target genes that regulate AD and VAD,The classifier based on target gene has sound diagnostic efficiency,The ability to distinguish between AD and VAD.The target gene based classifier can be used as a diagnostic prediction model,It yields a theoretical foundation for further research.