Gene Expression Data Analysis Of Alzheimer’s Disease On Etiology

Alzheimer’s disease is a common chronic disease with the progressive degenerative of the central nervous system, and its clinical characteristic are progressive memory loss,decline in cognitive function, behavior and social barriers, disease progression with a slow and irreversible disease course.Along with the aging of social population, the incidence of Alzheimer’s disease is on the rise. According to the statistics data, the prevalence of the elderly Alzheimer’s disease is in third place following cardiovascular disease and cancer, and at present there are nearly 36 million people around the world are suffering from AD. Nowadays, Alzheimer’s disease is still a terminally ill, and there are no treatments methods can make the patients recover. Alzheimer’s disease brings heavy burden to family and the society, and brings the patient himself great mental and physical pain.Alzheimer’s disease can occur in any age of adults, and of it presents exponential growth with the growth of age. The incidence is higher in women than in men, the rural people than the city people, and the incidence of people in high degree of education is relatively low.AD pathogenesis risk factors also include head trauma, low level sex hormone, family history, smoking, depression symptoms, the psychological pressure, vascular factor, low temperature, less social activities, mild cognitive impairment, virus infection and so on. Alzheimer’s disease lesions usually appear in hippocampus and entorhinal cortex of the limbic system, then spread to the temporal lobe, cingulated and parietal lobe of the frontal cortex area, generally does not spread to the occipital lobe, cerebellum, and motor and sensory cortex area. The brain pathological lesions of Alzheimer’s patients include nerve inflammatory senile plaques, neurofibrillary tangles, the loss of nerve cells and synapses, cerebral amyloid angioplasty and particle cavity deformation. The overall performance is diffuse cortical atrophy and ventricular enlargement.The pathogenesis of Alzheimer’s disease is still not clear. At present, molecular genetics and gene theory, inflammation doctrine, free radical theory, theory cholinergic, hypothesis of metal ions, viruses, oxidative stress theory and theory of estrogen levels are all involved. Most studies take a part for the whole, and can’t distinguish which mechanisms are the cause and which are the results. So many institutes and universities devote considerable resources to study the pathogenesis of AD,but the effect is not very ideal. Now it needs to know this disease from the whole macroscopic scale, and it cannot be affected by single one-sided effect of every mechanism. Also it needs to start from the gene expression, and to explore the pathogenesis of AD, treatments, as well as the method of early detection according to the differences of gene expression.Because of the complexity and limited sampling of the nerve cells, that choosing out age related genes on the level of gene expression has become the best way for the molecular pathogenesis research of Alzheimer’s disease.The Gene chip technology developed in recent years shows its superiority in genetic screening associated with genetic functional variations, and a few cases of sampling can get huge amounts of gene expression data, which will enhance the understanding of Alzheimer’s disease, and the data is more objective with high integrity.Currently, with the widespread application of high-throughput gene chip technology, the research institute and the laboratory have produced plenty of experimental data, but these data information is used for only a small part and all messages often have not been fully excavated. The Gene Expression Omnibus database established by National Center for Biotechnology Information is the largest, most complete, free-open public Gene Expression database, and it contains all kinds of complex biological data.These data seem disordered and unsystematic, but the vast amounts of biological data must contain important biology information, and these laws will be the key to the cause of explain Alzheimer’s disease.As we all know, in the gene expression spectrum there are thousands of data and tens of thousands of variables. Therefore, through Qlucore Omics Explorer (QOE) 3.0 bioinformatics software,the data can be fast conversed into three-dimensional visualization mages after statistical calculation, and then the structure and model hidden in the data are identified through the principal Component Analysis and cluster Analysis to get the differences and relationship between groups, data sets and samples in standard statistical methods. The common or differentially expressed genes are screened out and then the Gene Ontology Function enrichment analysis of gene list is conducted by the Annotation, the Visualization and Integrated Discovery (DAVID) 6.7 online Gene Annotation system in which the functions involved by gene are annotated, enrichment and clustered from the aspects of Cellular Component (CC), Biological Process(BP) and Molecular Function (MF).At last, the differences and changes in biology, the composition of cell and molecular function in patients with AD.Therefore, according to the current existing human Alzheimer’s disease gene expression profile datasets, this study aims to explore the pathogenesis of Alzheimer’s disease from the difference of whole gene expression, expression differences with age, the gene expression difference in different brain regions, the differences at different stages and gender related gene expression differences.Firstly, we analyzed GSE36980 by two-group comparisons and screened 196 differentially expressed genes from the brain of alzheimer’s patients and normal person. We cluster the GO terms and the results are divided into 42 annotation cluster, involving protein localization, ion transport, cell signaling, learning and memory, clathrin-coated vesicles, synapses, plasmic membrane, cell junction, mitochondria, calcium binding, ion channels, tau protein kinase, and fatty acid transport, etc. There is a connection between the different function and Alzheimer’s disease clinical symptoms and pathology. Results support the protein body damage compensation mechanism in brain neurons of Alzheimer’s disease. A substantial reduction in synapses and function is severely affected, and discovered the cause that Golgi is fracture in the brains of alzheimer’s patients and differentially expressed gene associated with the cause. The neuron membrane of Alzheimer’s disease is destroyed, and abnormal mitochondrial function damaged cell energy supply and produce excess free radicals. Anion channel and the metal cation are unusual that cause error in the information transmission and signal pathways. The genes’ expression of learning and memory changes in Alzheimer’s patients, which caused the fall of memory and cognitive function. Cytoskeleton and microtubules anomalies and also result in destruction of the three-dimensional space structure and the connection of neurons.It also showed the abnormal phosphorylation process, which will make the tau protein excess phosphorylation and become neurofibrillary tangles.The incidence of Alzheimer’s disease increases with age. Gene expression analysis of age related morbidity of the Alzheimer’s disease was studied.20 Alzheimer’s disease related gene expression data of GSE36980 and GSE53890 from GEO (Gene Expression Omnibus). Differentially expressed genes involved in Alzheimer’s disease and age were screened by two group comparison and linear regression in the case of strict compliance with statistical significance. The involved GO biological process of differentially expressed genes is mainly about protein metabolism, nerve metabolism, cell cycle regulation, axons, plasma membrane, synaptic, cytoskeleton, and metal ion binding. These are the reason that there is a positive correlation between weakened functions associated with age and Alzheimer’s disease. It also illustrated that the increasing age can lead to the brain atrophy, decrease functions of the brain, and similar alzheimer’s symptoms.The morbidity of different brain regions of Alzheimer’s disease is also different. This part we use GSE36980 and GSE9770 these two data sets.Though multi-group comparisons and two-group comparisons, we select 11 susceptibility genes which differentially expressed in various brain regions of Alzheimer’s disease. The main GO functions of these genes involved in cell polarity establishment or maintenance, ion binding, function of plasma membrane and calcium binding, which are related to signal transduction and information transfer function. The function of the limbic system is more active than other areas; this is the important reason for the susceptible of the limbic system and the disorders learning, emotion and memory after alzheimer’s disease. There are two genes CBLN4 and LRRTM1 are also age related alzheimer’s differentially expressed genes.Through rank regression analysis of GSE1297 data set, we found the differentially expressed genes with the aggravation of Alzheimer’s disease. This data set is a gene expression data of different disease state of hippocampus neuron.65 differentially expressed genes were screened,32 genes expressed high during the disease aggravate, and 33 genes expressed low. The high expressed genes are involved in transcriptional regulation, plasma membrane components, etc. The low expressed genes are related to mitochondrial function, protein localization and transport and nucleotide binding. Therefore, the AD patients should be taken in different treatment methods and doses based on their brain’s biological function change.The brains of men and women have certain differences in gene expression. To explore the cause of high morbidity on women in gene expression level, we selected Alzheimer’s disease of GSE36980 data sets and screened 26 differentially expressed genes by two-group comparisons. The involved GO biological functions of these genes are cytoskeleton, ion transfer, protein transport and location, nucleotide binding and membrane function. These functions of women are lower than men, which is one of the reasons that women more susceptible than men. Gene CBLN4 also showed in the list, which means that CBLN4 play an important role in the pathogenesis of Alzheimer’s disease.All these analysis of Alzheimer’s disease is based on the gene expression level. Differentially expressed genes and biological function were analyzed from the overall level of epidemiological statistics and pathological phenomena. Linking macroscopic with microscopic, our research provide objective theories for the prevention, diagnosis, research and treatment of Alzheimer’s disease.