ArticleFrontiers in aging neuroscience2022
Identification of Immune Hub Genes Associated With Braak Stages in Alzheimer's Disease and Their Correlation of Immune Infiltration.
Article in Frontiers in aging neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 14 citations in OpenAlex.
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- Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP/PS1 mice.Gut microbes · 2023Article
- Immune-related signature of periodontitis and Alzheimer's disease linkage.Frontiers in genetics · 2023Article
- Novel diagnostic biomarkers related to immune infiltration in Parkinson's disease by bioinformatics analysis.Frontiers in neuroscience · 2023Article
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4 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Background: Alzheimer'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. Methods: In 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. Results: Seven 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. Conclusion: The 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.
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