Identification of Immune Hub Genes Associated With Braak Stages in Alzheimer’s Disease and Their Correlation of Immune Infiltration
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...
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| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.887168/full |
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| author | Xiao-hang Qian Xiao-li Liu Sheng-di Chen Hui-dong Tang |
| author_facet | Xiao-hang Qian Xiao-li Liu Sheng-di Chen Hui-dong Tang |
| author_sort | Xiao-hang Qian |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T14:45:42Z |
| format | Article |
| id | doaj.art-a79980d1f8aa4b7aae7a178b37b32455 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-12T14:45:42Z |
| publishDate | 2022-05-01 |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-a79980d1f8aa4b7aae7a178b37b324552022-12-22T00:21:07ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-05-011410.3389/fnagi.2022.887168887168Identification of Immune Hub Genes Associated With Braak Stages in Alzheimer’s Disease and Their Correlation of Immune InfiltrationXiao-hang Qian0Xiao-li Liu1Sheng-di Chen2Hui-dong Tang3Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Shanghai, ChinaDepartment of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackgroundAlzheimer’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.https://www.frontiersin.org/articles/10.3389/fnagi.2022.887168/fullAlzheimer’s diseaseBraak stageimmune hub geneimmune cell infiltrationTau pathology |
| spellingShingle | Xiao-hang Qian Xiao-li Liu Sheng-di Chen Hui-dong Tang Identification of Immune Hub Genes Associated With Braak Stages in Alzheimer’s Disease and Their Correlation of Immune Infiltration Frontiers in Aging Neuroscience Alzheimer’s disease Braak stage immune hub gene immune cell infiltration Tau pathology |
| title | Identification of Immune Hub Genes Associated With Braak Stages in Alzheimer’s Disease and Their Correlation of Immune Infiltration |
| title_full | Identification of Immune Hub Genes Associated With Braak Stages in Alzheimer’s Disease and Their Correlation of Immune Infiltration |
| title_fullStr | Identification of Immune Hub Genes Associated With Braak Stages in Alzheimer’s Disease and Their Correlation of Immune Infiltration |
| title_full_unstemmed | Identification of Immune Hub Genes Associated With Braak Stages in Alzheimer’s Disease and Their Correlation of Immune Infiltration |
| title_short | Identification of Immune Hub Genes Associated With Braak Stages in Alzheimer’s Disease and Their Correlation of Immune Infiltration |
| title_sort | identification of immune hub genes associated with braak stages in alzheimer s disease and their correlation of immune infiltration |
| topic | Alzheimer’s disease Braak stage immune hub gene immune cell infiltration Tau pathology |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.887168/full |
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