Identification of crosstalk genes and immune characteristics between Alzheimer’s disease and atherosclerosis
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ABSTRACT:
SUBMITTER: An W
PROVIDER: S-EPMC11345154 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundProtein glycosylation has been confirmed to be involved in the pathological mechanisms of Alzheimer's disease (AD); however, there is still a lack of systematic analysis of the immune processes mediated by protein glycosylation-related genes (PGRGs) in AD.Materials and methodsTranscriptomic data of AD patients were obtained from the Gene Expression Omnibus database and divided into training and verification datasets. The core PGRGs of the training set were identified by weighted gene co-expression network analysis, and protein glycosylation-related subtypes in AD were identified based on k-means unsupervised clustering. Protein glycosylation scores and neuroinflammatory levels of different subtypes were compared, and functional enrichment analysis and drug prediction were performed based on the differentially expressed genes (DEGs) between the subtypes. A random forest model was used to select important DEGs as diagnostic markers between subtypes, and a line chart model was constructed and verified in other datasets. We evaluated the differences in immune cell infiltration between the subtypes through the single-sample gene set enrichment analysis, analyzed the correlation between core diagnostic markers and immune cells, and explored the expression regulation network of the core diagnostic markers.ResultsEight core PGRGs were differentially expressed between the training set and control samples. AD was divided into two subtypes with significantly different biological processes, such as vesicle-mediated transport in synapses and neuroactive ligand-receptor interactions. The high protein glycosylation subtype had a higher level of neuroinflammation. Riluzole and sulfasalazine were found to have potential clinical value in this subtype. A reliable construction line chart model was constructed based on nine diagnostic markers, and SERPINA3 was identified as the core diagnostic marker. There were significant differences in immune cell infiltration between the two subtypes. SERPINA3 was found to be closely related to immune cells, and the expression of SERPINA3 in AD was found to be regulated by a competing endogenous RNA network that involves eight long non-coding RNAs and seven microRNAs.ConclusionProtein glycosylation and its corresponding immune process play an important role in the occurrence and development of AD. Understanding the role of PGRGs in AD may provide a new potential therapeutic target for AD.
| S-EPMC9667030 | biostudies-literature
Project description:Autophagy is a protective and life-sustaining process in which cytoplasmic components are packaged into double-membrane vesicles and targeted to lysosomes for degradation. Accumulating evidence supports that autophagy is associated with several pathological conditions. However, research on the functional cross-links between autophagy and disease genes remains in its early stages. In this study, we constructed a disease-autophagy network (DAN) by integrating known disease genes, known autophagy genes and protein-protein interactions (PPI). Dissecting the topological properties of the DAN suggested that nodes that both autophagy and disease genes (inter-genes), are topologically important in the DAN structure. Next, a core network from the DAN was extracted to analyze the functional links between disease and autophagy genes. The genes in the core network were significantly enriched in multiple disease-related pathways, suggesting that autophagy genes may function in various disease processes. Of 17 disease classes, 11 significantly overlapped with autophagy genes, including cancer diseases, metabolic diseases and hematological diseases, a finding that is supported by the literatures. We also found that autophagy genes have a bridging role in the connections between pairs of disease classes. Altogether, our study provides a better understanding of the molecular mechanisms underlying human diseases and the autophagy process.
| S-EPMC5353691 | biostudies-literature
Project description:Periodontitis is an inflammatory and immune-related disease with links to several systemic diseases, and the pathological process of atherosclerosis also involves inflammatory and immune involvement. The aim of this study was to investigate the common immune cells and potential crosstalk genes between periodontitis (PD) and atherosclerosis (AS). By analyzing the weighted gene co-expression network of differentially immune infiltrating cells in two diseases to obtain important module genes, and taking the intersection of the module genes, we obtained 14 co-expressed immune-related genes, and evaluated the predictive value of 14 immune-related genes using three machine learning models.Two potential immune-related crosstalk genes (BTK and ITGAL) were finally obtained by taking intersections of WGCNA intersection genes, DEGs and IRGs.Then, the diagnostic column line graphs were constructed based on the 2 crosstalk genes, and the calibration curves, DCA curves and clinical impact curves indicated that the two genes had strong disease prediction ability, and we further validated the accuracy of the two potential crosstalk genes for disease diagnosis in the validation dataset.Single gene GSEA analysis showed that both genes are jointly involved in biological processes such as antigen presentation and immune regulation, and single sample GSEA analysis showed that macrophages and T cells play an important role in periodontitis in atherosclerosis.This study explored the genetic correlation between atherosclerosis and periodontitis using bioinformatics tools. BTK and ITGAL were found to be the most important crosstalk genes between the two diseases and may have an important role in the diagnosis and treatment of the diseases. Macrophage and T cell mediated inflammatory and immune responses may play an important role in periodontitis and atherosclerosis.
| S-EPMC10300131 | biostudies-literature
Project description:Currently, Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are widely prevalent in the elderly population, and accumulating evidence implies a strong link between them. For example, patients with T2DM have a higher risk of developing neurocognitive disorders, including AD, but the exact mechanisms are still unclear. This time, by combining bioinformatics analysis and in vivo experimental validation, we attempted to find a common biological link between AD and T2DM. We firstly downloaded the gene expression profiling (AD: GSE122063; T2DM: GSE161355) derived from the temporal cortex. To find the associations, differentially expressed genes (DEGs) of the two datasets were filtered and intersected. Based on them, enrichment analysis was carried out, and the least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms were used to identify the specific genes. After verifying in the external dataset and in the samples from the AD and type 2 diabetes animals, the shared targets of the two diseases were finally determined. Based on them, the ceRNA networks were constructed. Besides, the logistic regression and single-sample gene set enrichment analysis (ssGSEA) were performed. As a result, 62 DEGs were totally identified between AD and T2DM, and the enrichment analysis indicated that they were much related to the function of synaptic vesicle and MAPK signaling pathway. Based on the evidence from external dataset and RT-qPCR, CARTPT, EPHA5, and SERPINA3 were identified as the marker genes in both diseases, and their clinical significance and biological functions were further analyzed. In conclusion, discovering and exploring the marker genes that are dysregulated in both 2 diseases could help us better comprehend the intrinsic relationship between T2DM and AD, which may inspire us to develop new strategies for facing the dilemmas of clinical or basic research in cognitive dysfunction.
| S-EPMC9391608 | biostudies-literature
Project description:BackgroundAt present, there is a paucity of research on the link between Crohn's disease (CD) and atrial fibrillation (AF). Nevertheless, both ailments are thought to entail inflammatory and autoimmune processes, and emerging evidence indicates that individuals with CD may face an elevated risk of AF. To shed light on this issue, our study seeks to explore the possibility of shared genes, pathways, and immune cells between these two conditions.MethodsWe retrieved the gene expression profiles of both CD and AF from the Gene Expression Omnibus (GEO) database and subjected them to analysis. Afterward, we utilized the weighted gene co-expression network analysis (WGCNA) to identify shared genes, which were then subjected to further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Furthermore, we employed a rigorous analytical approach by screening hub genes through both least absolute shrinkage and selection operator (LASSO) regression and support vector machine (SVM), and subsequently constructing a receiver operating characteristic (ROC) curve based on the screening outcomes. Finally, we utilized single-sample gene set enrichment analysis (ssGSEA) to comprehensively evaluate the levels of infiltration of 28 immune cells within the expression profile and their potential association with the shared hub genes.ResultsUsing the WGCNA method, we identified 30 genes that appear to be involved in the pathological progression of both AF and CD. Through GO enrichment analysis on the key gene modules derived from WGCNA, we observed a significant enrichment of pathways related to major histocompatibility complex (MHC) and antigen processing. By leveraging the intersection of LASSO and SVM algorithms, we were able to pinpoint two overlapping genes, namely CXCL16 and HLA-DPB1. Additionally, we evaluated the infiltration of immune cells and observed the upregulation of CD4+ and CD8+ T cells, as well as dendritic cells in patients with AF and CD.ConclusionsBy employing bioinformatics tools, we conducted an investigation with the objective of elucidating the genetic foundations that connect AF and CD. This study culminated in the identification of CXCL16 and HLA-DPB1 as the most substantial genes implicated in the development of both disorders. Our findings suggest that the immune responses mediated by CD4+ and CD8+ T cells, along with dendritic cells, may hold a crucial role in the intricate interplay between AF and CD.
| S-EPMC10944785 | biostudies-literature
Project description:Alzheimer's disease (AD) is the most prevalent cause of dementia and is primarily associated with memory impairment and cognitive decline, but the etiology of AD has not been elucidated. In recent years, evidence has shown that immune cells play critical roles in AD pathology. In the current study, we collected the transcriptomic data of the hippocampus from gene expression omnibus database, and investigated the effect of immune cell infiltration in the hippocampus on AD, and analyzed the key genes that influence the pathogenesis of AD patients. The results revealed that the relative abundance of immune cells in the hippocampus of AD patients was altered. Of all given 28 kinds of immune cells, monocytes were the important immune cell associated with AD. We identified 4 key genes associated with both AD and monocytes, including KDELR1, SPTAN1, CDC16 and RBBP6, and they differentially expressed in 5XFAD mice and WT mice. The logistic regression and random forest models based on the 4 key genes could effectively distinguish AD from healthy samples. Our research provided a new perspective on immunotherapy for AD patients.
| S-EPMC10009990 | biostudies-literature
Project description:Alzheimer's disease (AD) is considered to one of 10 key diseases leading to death in humans. AD is considered the main cause of brain degeneration, and will lead to dementia. It is beneficial for affected patients to be diagnosed with the disease at an early stage so that efforts to manage the patient can begin as soon as possible. Most existing protocols diagnose AD by way of magnetic resonance imaging (MRI). However, because the size of the images produced is large, existing techniques that employ MRI technology are expensive and time-consuming to perform. With this in mind, in the current study, AD is predicted instead by the use of a support vector machine (SVM) method based on gene-coding protein sequence information. In our proposed method, the frequency of two consecutive amino acids is used to describe the sequence information. The accuracy of the proposed method for identifying AD is 85.7%, which is demonstrated by the obtained experimental results. The experimental results also show that the sequence information of gene-coding proteins can be used to predict AD.
| S-EPMC6321377 | biostudies-other
Project description:BackgroundAlzheimer's disease (AD) is the most common type of neurodegenerative disease. Tau pathology is one of the pathological features of AD, and its progression is closely related to the progress of AD. Immune system dysfunction is an important mediator of Tau pathological progression, but the specific molecular mechanism is still unclear. The purpose of this study is to determine the immune hub genes and peripheral immune cell infiltration associated with the Braak stages, and the molecular mechanisms between them.MethodsIn this study, 60 samples with different Braak stages in the GSE106241 dataset were used to screen Braak stages-related immune hub genes by using the WGCNA package in R and cytoHubba plugin. The temporal lobe expression data in the Alzdata database were used to verify the results. The correlation between the expression level of immune core genes and the pathological features of AD was analyzed to evaluate the abundance of peripheral immune cell infiltration and screened Braak stages-related cells. Finally, we used correlation analysis of immune hub genes and immune cells and Gene Set Enrichment Analysis (GSEA) of them.ResultsSeven genes (GRB2, HSP90AA1, HSPA4, IGF1, KRAS, PIK3R1, and PTPN11) were identified as immune core genes after the screening of the test datasets and validation of independent data. Among them, Kirsten rat sarcoma viral oncogene homolog (KRAS) and Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1) were the most closely related to Tau and Aβ pathology in AD. In addition, the ImmuneScore increased gradually with the increase of Braak stages. Five types of immune cells (plasma cells, T follicular helper cells, M2 macrophage, activated NK cells, and eosinophils) were correlated with Braak stages. KRAS and PIK3R1 were the immune core genes most related to the abnormal infiltration of peripheral immune cells. They participated in the regulation of the pathological process of AD through axon guidance, long-term potentiation, cytokine-cytokine receptor interaction, RNA polymerase, etc.ConclusionThe KRAS and PIK3R1 genes were identified as the immune hub genes most associated with Tau pathological progress in AD. The abnormal infiltration of peripheral immune cells mediated by these cells was involved in the Tau pathological process. This provides new insights for AD.
| S-EPMC9129065 | biostudies-literature
Project description:Alzheimer's disease (AD) is a neurodegenerative disease that involves multiple systems in the body. Numerous recent studies have revealed bidirectional crosstalk between the brain and bone, but the interaction between bone and brain in AD remains unclear. In this review, we summarize human studies of the association between bone and brain and provide an overview of their interactions and the underlying mechanisms in AD. We review the effects of AD on bone from the aspects of AD pathogenic proteins, AD risk genes, neurohormones, neuropeptides, neurotransmitters, brain-derived extracellular vesicles (EVs), and the autonomic nervous system. Correspondingly, we elucidate the underlying mechanisms of the involvement of bone in the pathogenesis of AD, including bone-derived hormones, bone marrow-derived cells, bone-derived EVs, and inflammation. On the basis of the crosstalk between bone and the brain, we propose potential strategies for the management of AD with the hope of offering novel perspectives on its prevention and treatment. HIGHLIGHTS: The pathogenesis of AD, along with its consequent changes in the brain, may involve disturbing bone homeostasis. Degenerative bone disorders may influence the progression of AD through a series of pathophysiological mechanisms. Therefore, relevant bone intervention strategies may be beneficial for the comprehensive management of AD.
| S-EPMC11350061 | biostudies-literature
Project description:Alzheimer's disease (AD), a neurodegenerative diseases (neuro-diseases) which is prevalent in the elderly and seriously affects the lives of individuals. Many studies have discussed the relationship between immune system and AD pathogenesis. Here, the meta-analysis of differentially expressed (DE) genes based on microarray data was conducted to study the association between AD and immune system. 9519 target genes of hippocampus in 146 subjects (73 AD cases and 73 controls) from 4 microarray data sets were compiled and DE genes with p < 1.00E - 04 were selected to conduct the pathway-analysis. The results indicated that the DE genes were significantly enriched in the neuro-diseases as well as the immune system pathways.
| S-EPMC6344412 | biostudies-literature