A Study On The Correlation Between Brain Functional Connections And Genetic Mutations In Alzheimer’s Disease

Alzheimer’s disease(AD)is one of the most common human neurodegenerative diseases and is often directly affected by a variety of genes and genetic variations.Currently,this neuroprogressive and irreversible degenerative disease of nerve damage in the human brain is listed by the ministry of health as the fourth most common cause of disease and risk of death.Some researchers believe that Mild cognitive impairment(MCI)is an intermediate state from Normal Control(NC)to AD,and more than 50% of MCI patients will convert to AD,and some MCI patients can remain stable or even recover to NC.Therefore,it is extremely necessary to discover abnormal features of early AD and study computer-aided automatic,efficient and accurate methods to achieve early diagnosis and intervention of dementia.At present,the research on the pathogenesis of AD has not been unified at home and abroad,so it is still a hot topic to search for reliable indicators of early diagnosis of AD.In recent years,with the deepening of the graph theory analysis and complex network research based on functional Magnetic Resonance Imaging(f MRI),the quantitative analysis of abnormal brain neural activity and the search for biomarkers in AD spectrum population have been provided with technical guarantee.At the same time,scholars at home and abroad have found that there are different functional modules in human brain during infancy,and its topological properties more accurately reflect the changes of information communication patterns and organizational rules between brain modules.In recent years,genetic factors have been widely recognized by the medical community as an important indicator for the earliest accurate prediction and judgment of the risk of AD,and a large number of scholars have confirmed the high clinical heritability of people with AD through the results of twin studies.In the early screening of genetic risk factors for AD,genome-wide Association analysis(Genome-Wide Association Studies,GWAS)combined with pathogenic biological phenotype analysis,and then found in the development of AD disease with the mutated gene disease risk,its basic principle is to take all SNPs for risk assessment of genetic disease,early in the filter with ordinary genetic effect weak coverage and disease risk gene variant has strong advantage.Thus,this study made full use of the advantages of the GWAS study,and combined with the biological phenotype analysis,found the pathogenic risk mutation gene of AD.Therefore,this study divided the subjects into NC,MCI and AD according to the diagnostic group.Based on the association analysis of whole genome combined with graph theory,this study searched for the variant genes associated with the brain functional network activity in the whole genome of the subjects of alzheimer’s disease pedigree,and analyzed the abnormal development rule of the brain neural activity under the influence of the mutation gene and its influence on the development of AD disease.It provides a basis for the research of adjunctive diagnosis and treatment of AD spectrum diseases.The main contents and results of this study mainly include:(1)Construction of functional brain network and quantitative analysisThe quantitative analysis method of complex brain functional network based on graph theory analysis can be widely used in the study of brain functional network and organization.The analysis of its topological structure features is of great scientific value and can effectively and directly reflect the abnormality of complex brain functional network connection.Therefore,this paper studies the topological structure analysis of brain functional network based on automated evaluation labeling(AAL),and USES MATLAB to calculate the topological structure attribute of brain network based on binary adjacency matrix,so as to achieve the purpose of quantitative analysis of brain network.(2)Correlation analysis between whole gene and brain network index based on graph theoryTargeted on the AD patients have high genetic heritage,and the current study pathogenic genes of risk analysis in the early of AD were often ignore the potential risk of interaction between genetic and phenotypic variation,will result in a lost and the potential risk of neurological diseases pathogenic gene loci of abnormal situation,so this research take the GWAS as further study of the pathogenesis of AD early important analysis method.On the other hand,functional magnetic resonance imaging(fmri)can present the changes of neural activity of brain diseases in a timely manner.Therefore,this study proposed for the first time that GWAS was combined with functional brain network index to find the risk mutation gene of early AD.(3)Analyze the influence of different genotypes on indexes of brain network and module networkIn view of the current lack of AD brain connection module spectrum crowd in the study of information communication under the network analysis and study of the impact of pathogenic gene loci,this topic research under the condition of considering the genotyping,AD is put forward to develop the crowd of brain function to connect to the Internet modular,fully consider each function module brain connections between information exchange network function changes.Firstly,according to the different genotypes of PDE4 D,the researchers conducted statistical analysis and test on the brain network between two subjects and the topological network properties under their modules respectively,and analyzed the direct influence of the wild type and variant type of PDE4 D on the whole brain connection network and the topological properties of the module sub-network in early AD pedigree population.(4)To analyze the influence of target genotyping of wild type and variant type on the classification accuracy of NC,MCI and ADIn order to analyze the whole brain and module network topological properties in the target gene PDE4 D under the influence of the wild-type and variant for early diagnosis of AD differences,the researchers extracted the diagnosis of significant differences between groups under different genotypes of brain network attribute characteristics,using the SVM classification,classification test: after joining genetically variable network index classification accuracy vs.no genetically variable network indicators classification accuracy is analyzed under the influence of different target PDE4 D genotype subjects network index classification accuracy of the differences between groups.The results of this step showed that the classification accuracy was significantly improved after the target gene of PDE4 D and the subject group with variant gene were refined.To sum up,this study compared the diagnosis group of people of AD spectrum in pairs,compared and analyzed the functional brain network properties of people with PDE4 D variant genotype and people with PDE4 D wild type,and extracted the characteristics of significant differences between the diagnosis groups and added them into the auxiliary diagnosis of diseases.Consistent research results show that the PDE4 D genotype directly affects the normal activity of the functional network nerves in early AD.If the importance of the PDE4 D genotype on disease diagnosis in early AD population can be fully considered in subsequent clinical studies,the accuracy of classification may be further improved.