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Analysis of transcription factor- and ncRNA-mediated potential pathogenic gene modules in Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is a progressive neurodegenerative disease that ranks as the fourth most common cause of death in developed countries. In our study, genes differentially expressed between AD and healthy individuals were identified and used to construct protein-protein interaction (PPI) networks. The AD-related PPI network was used to identify functional modules, and enrichment analysis showed that they were significantly involved in "Alzheimer's disease", "apoptosis", and related pathways. We predicted non-coding RNAs and transcription factors that may regulate the functional modules. The expression of hub genes and transcription factors was validated in an independent data set. The results in this study provide several candidates for further research on mechanisms of AD pathogenesis.

SUBMITTER: Zou C

PROVIDER: S-EPMC6738443 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Analysis of transcription factor- and ncRNA-mediated potential pathogenic gene modules in Alzheimer's disease.

Zou Cuihua C Wang Jie J Huang Xiaohua X Jian Chongdong C Zou Donghua D Li Xuebin X

Aging 20190816 16

Alzheimer's disease (AD) is a progressive neurodegenerative disease that ranks as the fourth most common cause of death in developed countries. In our study, genes differentially expressed between AD and healthy individuals were identified and used to construct protein-protein interaction (PPI) networks. The AD-related PPI network was used to identify functional modules, and enrichment analysis showed that they were significantly involved in "Alzheimer's disease", "apoptosis", and related pathwa ...[more]

PMID: 31422384

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Project description:BackgroundAlzheimer's disease (AD) is a pervasive age-related and highly heritable neurodegenerative disorder but has no effective therapy. The complex cellular microenvironment in the AD brain impedes our understanding of pathogenesis. Thus, a comprehensive investigation of cell type-specific responses in AD is crucial to provide precise molecular and cellular targets for therapeutic development.MethodsHere, we integrated analyzed 4,441 differentially expressed genes (DEGs) that were identified from 263,370 single-cells in cortex samples by single-nucleus RNA sequencing (snRNA-seq) between 42 AD-pathology subjects and 39 normal controls within 3 studies. DEGs were analyzed in microglia, astrocytes, oligodendrocytes, excitatory neurons, inhibitory neurons, and endothelial cells, respectively. In each cell type, we identified both common DEGs which were observed in all 3 studies, and overlapping DEGs which have been seen in at least 2 studies. Firstly, we showed the common DEGs expression and explained the biological functions by comparing with existing literature or multil-omics signaling pathways knowledgebase. We then determined the significant modules and hub genes, and explored the biological processes using the overlapping DEGs. Finally, we identified the common and distinct dysregulated pathways using overall DEGs and overlapping DEGs in a cell type-specific manner.ResultsUp-regulated LINGO1 has been seen in both oligodendrocytes and excitatory neurons across 3 studies. Interestingly, genes enriched in the mitochondrial module were up-regulated across all cell types, which indicates mitochondrial dysfunction in the AD brain. The estrogen signaling pathway seems to be the most common pathway that is disrupted in AD.ConclusionTogether, these analyses provide detailed information of cell type-specific and overall transcriptional changes and pathways underlying the human AD-pathology. These findings may provide important insights for drug development to tackle this disease.

Dataset Information

Analysis of transcription factor- and ncRNA-mediated potential pathogenic gene modules in Alzheimer's disease.

Publications

Analysis of transcription factor- and ncRNA-mediated potential pathogenic gene modules in Alzheimer's disease.

Similar Datasets

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