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• W2022222956 abstract "The induction of an antibody response to amyloid beta (Abeta) peptide has become a strategy for the treatment of Alzheimer's disease (AD). This has proven effective in reducing the plaque burden in transgenic mice that develop Abeta plaques similar to human AD patients. The mechanism for enhanced clearance of Abeta is partly due to the interaction of immunoglobulin Fcgamma receptor-expressing microglia and specific antibody-opsonized Abeta deposits. This interaction can stimulate Fcgamma receptor-mediated phagocytosis, but also results in inflammatory activation of these cells. Consequently, interaction of microglia with antibody-antigen complexes could exacerbate the existing inflammation in the brains of AD patients. In this study, we used substrate-bound Abeta and cultured human microglia from AD and non-demented cases to model interaction of microglia and antibody-opsonized plaques in AD brains. Enhanced production of tumor necrosis factor-alpha, macrophage colony stimulating factor, interleukin-10, and superoxide ions was detected. We also demonstrated enhanced uptake of opsonized Abeta by microglia, which was reduced significantly in the presence of excess IgG, indicative of the involvement of Fcgamma receptor-mediated mechanisms. Human microglia were shown in this study to express mRNA for Fcgamma receptors I, IIa, IIb, and III. The expression of Fcgamma receptor II was augmented by proinflammatory stimulation. These results suggest that initial interactions of human microglia with antibody-opsonized amyloid could result in increased inflammation. The consequence of this on inflammatory pathology in AD brains needs to be considered before immunization is used as a strategy for treating AD." @default.
• W2022222956 created "2016-06-24" @default.
• W2022222956 creator A5022856463 @default.
• W2022222956 creator A5059245617 @default.
• W2022222956 date "2002-10-25" @default.
• W2022222956 modified "2023-09-23" @default.
• W2022222956 title "Modeling Alzheimer's disease immune therapy mechanisms: Interactions of human postmortem microglia with antibody-opsonized amyloid beta peptide" @default.
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• W2022222956 doi "https://doi.org/10.1002/jnr.10422" @default.
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