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Transcriptional Networks of Microglia in Alzheimer's Disease and Insights into Pathogenesis
Gabriel Chew1, Enrico Petretto2
1Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, 69857 Singapore, Singapore. e0008504@u.nus.edu.
Abstract:
Microglia, the main immune cells of the central nervous system, are increasingly implicated in Alzheimer's disease (AD). Manifold transcriptomic studies in the brain have not only highlighted microglia's role in AD pathogenesis, but also mapped crucial pathological processes and identified new therapeutic targets. An important component of many of these transcriptomic studies is the investigation of gene expression networks in AD brain, which has provided important new insights into how coordinated gene regulatory programs in microglia (and other cell types) underlie AD pathogenesis. Given the rapid technological advancements in transcriptional profiling, spanning from microarrays to single-cell RNA sequencing (scRNA-seq), tools used for mapping gene expression networks have evolved to keep pace with the unique features of each transcriptomic platform. In this article, we review the trajectory of transcriptomic network analyses in AD from brain to microglia, highlighting the corresponding methodological developments. Lastly, we discuss examples of how transcriptional network analysis provides new insights into AD mechanisms and pathogenesis.
Insights
Microglia play a key role in Alzheimer's disease (AD) pathogenesis. Transcriptomic network analysis in the AD brain reveals crucial gene expression patterns and therapeutic targets, advancing our understanding of disease mechanisms.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia are central nervous system immune cells implicated in Alzheimer's disease (AD) pathogenesis.
- Transcriptomic studies in the AD brain have identified microglia's role and potential therapeutic targets.
- Gene expression networks offer insights into coordinated gene regulation in AD.
Purpose of the Study:
- To review transcriptomic network analyses in AD, focusing on brain and microglia.
- To highlight methodological advancements in analyzing gene expression data.
- To discuss the application of these analyses in understanding AD mechanisms.
Main Methods:
- Review of transcriptomic studies in Alzheimer's disease brain.
- Analysis of gene expression networks, including microarrays and single-cell RNA sequencing (scRNA-seq).
- Methodological comparison of tools for transcriptomic data analysis.
Main Results:
- Transcriptomic studies have mapped key pathological processes in AD involving microglia.
- Gene expression network analysis provides insights into coordinated gene regulatory programs.
- Advancements in transcriptional profiling technologies enable more detailed network mapping.
Conclusions:
- Transcriptional network analysis is a powerful tool for understanding AD pathogenesis.
- The evolution of transcriptomic technologies has enhanced the study of gene networks in AD.
- Further application of these methods promises new discoveries in AD mechanisms and therapeutics.
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