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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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Autores principales: Jian, Chongdong, Wei, Lei, Mo, Ruikang, Li, Rongjie, Liang, Lucong, Chen, Liechun, Zou, Chun, Meng, Youshi, Liu, Ying, Zou, Donghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488208/
https://www.ncbi.nlm.nih.gov/pubmed/34616287
http://dx.doi.org/10.3389/fnagi.2021.731180
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author Jian, Chongdong
Wei, Lei
Mo, Ruikang
Li, Rongjie
Liang, Lucong
Chen, Liechun
Zou, Chun
Meng, Youshi
Liu, Ying
Zou, Donghua
author_facet Jian, Chongdong
Wei, Lei
Mo, Ruikang
Li, Rongjie
Liang, Lucong
Chen, Liechun
Zou, Chun
Meng, Youshi
Liu, Ying
Zou, Donghua
author_sort Jian, Chongdong
collection PubMed
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.
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spelling pubmed-84882082021-10-05 Microglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication Jian, Chongdong Wei, Lei Mo, Ruikang Li, Rongjie Liang, Lucong Chen, Liechun Zou, Chun Meng, Youshi Liu, Ying Zou, Donghua Front Aging Neurosci Neuroscience 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. Frontiers Media S.A. 2021-09-20 /pmc/articles/PMC8488208/ /pubmed/34616287 http://dx.doi.org/10.3389/fnagi.2021.731180 Text en Copyright © 2021 Jian, Wei, Mo, Li, Liang, Chen, Zou, Meng, Liu and Zou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Jian, Chongdong
Wei, Lei
Mo, Ruikang
Li, Rongjie
Liang, Lucong
Chen, Liechun
Zou, Chun
Meng, Youshi
Liu, Ying
Zou, Donghua
Microglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication
title 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_short 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
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488208/
https://www.ncbi.nlm.nih.gov/pubmed/34616287
http://dx.doi.org/10.3389/fnagi.2021.731180
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