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Updated: Oct 7, 2025
Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing
Published on: December 3, 2019
Microglia Heterogeneity in Alzheimer's Disease: Insights From Single-Cell Technologies
1Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Abstract:
Microglia are resident immune cells in the central nervous system and play critical roles in brain immunity, development, and homeostasis. The pathology of Alzheimer's disease (AD) triggers activation of microglia. Microglia express many AD risk genes, suggesting that their response to AD pathology can affect disease progression. Microglia have long been considered a homogenous cell population. The diversity of microglia has gained great interest in recent years due to the emergence of novel single-cell technologies, such as single-cell/nucleus RNA sequencing and single-cell mass cytometry by time-of-flight. This review summarizes the current knowledge about the diversity/heterogeneity of microglia and distinct microglia states in the brain of both AD mouse models and patients, as revealed by single-cell technologies. It also discusses the future developments for application of single-cell technologies and the integration of these technologies with functional studies to further dissect microglia biology in AD. Defining the functional correlates of distinct microglia states will shed new light on the pathological roles of microglia and might uncover new relevant therapeutic targets for AD.
Insights
Microglia, the brain's immune cells, show diverse states in Alzheimer's disease (AD). Understanding these distinct microglia populations is key to developing new AD therapies.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia are key immune cells in the central nervous system, crucial for brain homeostasis and immunity.
- Alzheimer's disease (AD) pathology activates microglia, and their response influences disease progression.
- Previously considered a uniform population, microglia diversity is now a major research focus.
Purpose of the Study:
- To review current knowledge on microglia diversity and distinct states in Alzheimer's disease.
- To highlight the impact of single-cell technologies in revealing microglia heterogeneity in AD.
- To discuss future directions for integrating single-cell technologies with functional studies in AD research.
Main Methods:
- Utilizing single-cell technologies like single-cell/nucleus RNA sequencing.
- Analyzing single-cell mass cytometry by time-of-flight.
- Reviewing data from both Alzheimer's disease mouse models and human patients.
Main Results:
- Single-cell technologies reveal significant diversity and distinct states among microglia in AD brains.
- Identification of specific microglia populations associated with AD pathology.
- Evidence suggests microglia heterogeneity plays a role in AD pathogenesis.
Conclusions:
- Microglia are not a homogenous population and exhibit diverse states in Alzheimer's disease.
- Single-cell technologies are powerful tools for dissecting microglia heterogeneity in AD.
- Understanding distinct microglia states may reveal novel therapeutic targets for AD.
