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Updated: Aug 16, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglial responses to amyloid beta peptide opsonization and indomethacin treatment
Ronald Strohmeyer1, Carl J Kovelowski, Diego Mastroeni
1L.J. Roberts Center, Sun Health Research Institute, Sun City, AZ 85351, USA. RWStrohmeyer@NNU.edu
Background:
Recent studies have suggested that passive or active immunization with anti-amyloid beta peptide (Abeta) antibodies may enhance microglial clearance of Abeta deposits from the brain. However, in a human clinical trial, several patients developed secondary inflammatory responses in brain that were sufficient to halt the study.
Methods:
We have used an in vitro culture system to model the responses of microglia, derived from rapid autopsies of Alzheimer's disease patients, to Abeta deposits.
Results:
Opsonization of the deposits with anti-Abeta IgG 6E10 enhanced microglial chemotaxis to and phagocytosis of Abeta, as well as exacerbated microglial secretion of the pro-inflammatory cytokines TNF-alpha and IL-6. Indomethacin, a common nonsteroidal anti-inflammatory drug (NSAID), had no effect on microglial chemotaxis or phagocytosis, but did significantly inhibit the enhanced production of IL-6 after Abeta opsonization.
Conclusion:
These results are consistent with well known, differential NSAID actions on immune cell functions, and suggest that concurrent NSAID administration might serve as a useful adjunct to Abeta immunization, permitting unfettered clearance of Abeta while dampening secondary, inflammation-related adverse events.
Insights
Anti-amyloid beta peptide (Abeta) immunization may clear brain deposits, but can cause inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce this inflammation, allowing safe Abeta clearance for Alzheimer's disease treatment.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Emerging research suggests anti-amyloid beta peptide (Abeta) antibodies can enhance microglial clearance of Abeta deposits.
- However, clinical trials were halted due to severe secondary inflammatory responses in patients.
Purpose of the Study:
- To investigate microglial responses to Abeta deposits in an in vitro model.
- To explore the potential of nonsteroidal anti-inflammatory drugs (NSAIDs) to mitigate inflammation during Abeta immunotherapy.
Main Methods:
- Utilized an in vitro culture system with microglia from Alzheimer's disease patient autopsies.
- Opsonized Abeta deposits with anti-Abeta IgG 6E10 and assessed microglial chemotaxis, phagocytosis, and cytokine secretion.
- Investigated the effect of indomethacin, an NSAID, on these microglial responses.
Main Results:
- Opsonization enhanced microglial chemotaxis and phagocytosis of Abeta.
- Pro-inflammatory cytokine secretion (TNF-alpha and IL-6) was exacerbated by Abeta opsonization.
- Indomethacin did not affect microglial chemotaxis or phagocytosis but significantly inhibited IL-6 production.
Conclusions:
- NSAID actions on immune cells are differential, impacting cytokine production.
- Concurrent NSAID administration may be a valuable adjunct to Abeta immunization.
- NSAIDs could enable Abeta clearance while suppressing inflammation-related adverse events.
