Microglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication
Alzheimer’s disease (AD) is a common neurodegenerative disease. Its onset is insidious and its progression is slow, making diagnosis difficult. In addition, its underlying molecular and cellular mechanisms remain unclear. In this study, clustering analysis was performed on single-cell RNA sequencing...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:ccff65045d6441f2ae64b67e61b98f4f2021-11-18T15:33:02ZMicroglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication1663-436510.3389/fnagi.2021.731180https://doaj.org/article/ccff65045d6441f2ae64b67e61b98f4f2021-09-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.731180/fullhttps://doaj.org/toc/1663-4365Alzheimer’s disease (AD) is a common neurodegenerative disease. Its onset is insidious and its progression is slow, making diagnosis difficult. In addition, its underlying molecular and cellular mechanisms remain unclear. In this study, clustering analysis was performed on single-cell RNA sequencing (scRNA-seq) data from the prefrontal cortex of 48 AD patients. Each sample module was identified to be a specific AD cell type, eight main brain cell types were identified, and the dysfunctional evolution of each cell type was further explored by pseudo-time analysis. Correlation analysis was then used to explore the relationship between AD cell types and pathological characteristics. In particular, intercellular communication between neurons and glial cells in AD patients was investigated by cell communication analysis. In patients, neuronal cells and glial cells significantly correlated with pathological features, and glial cells appear to play a key role in the development of AD through ligand-receptor axis communication. Marker genes involved in communication between these two cell types were identified using five types of modeling: logistic regression, multivariate logistic regression, least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). LASSO modeling identified CXCR4, EGFR, MAP4K4, and IGF1R as key genes in this communication. Our results support the idea that microglia play a role in the occurrence and development of AD through ligand-receptor axis communication. In particular, our analyses identify CXCR4, EGFR, MAP4K4, and IGF1R as potential biomarkers and therapeutic targets in AD.Chongdong JianLei WeiRuikang MoRongjie LiLucong LiangLiechun ChenChun ZouYoushi MengYing LiuYing LiuDonghua ZouFrontiers Media S.A.articleAlzheimer’s diseaseintercellular communicationreceptor ligand axisLASSOsupport vector machineNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021) |
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| collection |
DOAJ |
| language |
EN |
| topic |
Alzheimer’s disease intercellular communication receptor ligand axis LASSO support vector machine Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 |
| spellingShingle |
Alzheimer’s disease intercellular communication receptor ligand axis LASSO support vector machine Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Chongdong Jian Lei Wei Ruikang Mo Rongjie Li Lucong Liang Liechun Chen Chun Zou Youshi Meng Ying Liu Ying Liu Donghua Zou Microglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication |
| description |
Alzheimer’s disease (AD) is a common neurodegenerative disease. Its onset is insidious and its progression is slow, making diagnosis difficult. In addition, its underlying molecular and cellular mechanisms remain unclear. In this study, clustering analysis was performed on single-cell RNA sequencing (scRNA-seq) data from the prefrontal cortex of 48 AD patients. Each sample module was identified to be a specific AD cell type, eight main brain cell types were identified, and the dysfunctional evolution of each cell type was further explored by pseudo-time analysis. Correlation analysis was then used to explore the relationship between AD cell types and pathological characteristics. In particular, intercellular communication between neurons and glial cells in AD patients was investigated by cell communication analysis. In patients, neuronal cells and glial cells significantly correlated with pathological features, and glial cells appear to play a key role in the development of AD through ligand-receptor axis communication. Marker genes involved in communication between these two cell types were identified using five types of modeling: logistic regression, multivariate logistic regression, least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). LASSO modeling identified CXCR4, EGFR, MAP4K4, and IGF1R as key genes in this communication. Our results support the idea that microglia play a role in the occurrence and development of AD through ligand-receptor axis communication. In particular, our analyses identify CXCR4, EGFR, MAP4K4, and IGF1R as potential biomarkers and therapeutic targets in AD. |
| format |
article |
| author |
Chongdong Jian Lei Wei Ruikang Mo Rongjie Li Lucong Liang Liechun Chen Chun Zou Youshi Meng Ying Liu Ying Liu Donghua Zou |
| author_facet |
Chongdong Jian Lei Wei Ruikang Mo Rongjie Li Lucong Liang Liechun Chen Chun Zou Youshi Meng Ying Liu Ying Liu Donghua Zou |
| author_sort |
Chongdong Jian |
| title |
Microglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication |
| title_short |
Microglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication |
| title_full |
Microglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication |
| title_fullStr |
Microglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication |
| title_full_unstemmed |
Microglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication |
| title_sort |
microglia mediate the occurrence and development of alzheimer’s disease through ligand-receptor axis communication |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/ccff65045d6441f2ae64b67e61b98f4f |
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