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Updated: Nov 2, 2025
Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
Published on: June 1, 2016
Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivo
Karen N McFarland1,2,3, Carolina Ceballos2,3,4, Awilda Rosario2,3,4
1Department of Neurology, University of Florida, Gainesville, FL, USA knmcfarland@ufl.edu.
Abstract:
Aggregation and accumulation of amyloid-β (Aβ) is a defining feature of Alzheimer's disease pathology. To study microglial responses to Aβ, we applied exogenous Aβ peptide, in either oligomeric or fibrillar conformation, to primary mouse microglial cultures and evaluated system-level transcriptional changes and then compared these with transcriptomic changes in the brains of CRND8 APP mice. We find that primary microglial cultures have rapid and massive transcriptional change in response to Aβ. Transcriptomic responses to oligomeric or fibrillar Aβ in primary microglia, although partially overlapping, are distinct and are not recapitulated in vivo where Aβ progressively accumulates. Furthermore, although classic immune mediators show massive transcriptional changes in the primary microglial cultures, these changes are not observed in the mouse model. Together, these data extend previous studies which demonstrate that microglia responses ex vivo are poor proxies for in vivo responses. Finally, these data demonstrate the potential utility of using microglia as biosensors of different aggregate conformation, as the transcriptional responses to oligomeric and fibrillar Aβ can be distinguished.
Insights
Microglia exhibit distinct transcriptional responses to different amyloid-beta (Aβ) forms in culture, but these changes differ from those observed in Alzheimer's disease mouse models. This suggests microglia can act as biosensors for Aβ conformation.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) aggregation.
- Microglia, the brain's immune cells, are implicated in AD pathogenesis.
- Understanding microglial responses to Aβ is crucial for AD research.
Purpose of the Study:
- To investigate microglial transcriptional responses to different amyloid-beta (Aβ) conformations (oligomeric vs. fibrillar).
- To compare ex vivo microglial responses with in vivo transcriptomic changes in an Alzheimer's disease mouse model.
- To assess the potential of microglia as biosensors for Aβ aggregate conformation.
Main Methods:
- Primary mouse microglial cultures were exposed to oligomeric or fibrillar Aβ.
- System-level transcriptional changes in microglia were analyzed.
- Transcriptomic data were compared with those from CRND8 APP mouse brains.
Main Results:
- Primary microglia showed rapid, massive transcriptional changes in response to Aβ.
- Transcriptional responses to oligomeric and fibrillar Aβ were distinct, with partial overlap.
- Ex vivo microglial responses did not fully recapitulate in vivo changes observed in the mouse model.
- Classic immune mediator changes seen in culture were absent in the mouse model.
Conclusions:
- Microglial responses in vitro are not accurate proxies for in vivo responses in Alzheimer's disease.
- Distinct transcriptional profiles indicate microglia can differentiate between Aβ aggregate conformations.
- This highlights the potential of microglia as biosensors for Aβ conformation in neurological diseases.
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