Research

Microglial responses to amyloid β peptide opsonization and indomethacin treatment

Ronald Strohmeyer , Carl J Kovelowski , Diego Mastroeni , Brian Leonard , Andrew Grover and Joseph Rogers

L.J. Roberts Center, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351 USA

author email corresponding author email

Journal of Neuroinflammation 2005, 2:18doi:10.1186/1742-2094-2-18

Published:	19 August 2005

Abstract

Background

Recent studies have suggested that passive or active immunization with anti-amyloid β peptide (Aβ) antibodies may enhance microglial clearance of Aβ 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 Aβ deposits.

Results

Opsonization of the deposits with anti-Aβ IgG 6E10 enhanced microglial chemotaxis to and phagocytosis of Aβ, as well as exacerbated microglial secretion of the pro-inflammatory cytokines TNF-α 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 Aβ 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 Aβ immunization, permitting unfettered clearance of Aβ while dampening secondary, inflammation-related adverse events.