Microglial responses to amyloid beta peptide opsonization and indomethacin treatment

Background: Recent studies have suggested that passive or active immunization with anti-amyloid beta peptide (A beta) antibodies may enhance microglial clearance of A beta 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 A beta deposits. Results: Opsonization of the deposits with anti-A beta IgG 6E10 enhanced microglial chemotaxis to and phagocytosis of A beta, 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 A beta 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 A beta immunization, permitting unfettered clearance of A beta while dampening secondary, inflammation-related adverse events.