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Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
Published on: June 14, 2020
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Basic Science and Pathogenesis.
Anuragh Sriram1, Matthew Sadgrove1, Gwenn A Garden1
1University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
Summary
The phospholipase C gamma 2 (PLCG2)-P522R variant reduces NLRP3 inflammasome activation in microglia, potentially lowering Alzheimer's disease (AD) risk. This study offers a new method for measuring inflammasome activity and supports NLRP3-targeted AD therapies.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- GWAS identified a link between the PLCG2-P522R variant and reduced Alzheimer's disease (AD) risk.
- PLCG2 is expressed in microglia, the brain's immune cells, and its P522R variant shows enhanced activity.
- The NLRP3 inflammasome in microglia is implicated in AD neuroinflammation and amyloid-beta (Aβ) aggregation.
Purpose of the Study:
- To investigate the role of PLCG2-P522R in modulating NLRP3 inflammasome activation.
- To explore the potential mechanism by which P522R confers protection against AD pathology.
Main Methods:
- Cultured mouse microglia (WT, P522R+/- , P522R+/+).
- Stimulated microglia with LPS and Aβ.
- Quantified ASC speck formation and secretion using flow cytometry and microscopy.
Main Results:
- P522R+/+ microglia exhibited reduced ASC speck formation and secretion upon Aβ exposure compared to WT.
- P522R+/- microglia did not show this reduction.
- Aβ exposure alone mimicked inflammasome activation seen with LPS + Aβ treatment.
Conclusions:
- PLCG2-P522R activation of the NLRP3 inflammasome in microglia is reduced.
- This reduction may explain the association between P522R and decreased AD risk.
- A novel flow cytometry method for quantifying secreted ASC specks was developed, supporting NLRP3-targeted AD therapeutics.
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