A beta-Induce inflammatory processes in microglia cells of APP23 transgenic mice

A microglial response is part of the inflammatory processes in Alzheimer's disease (AD). We have used APP23 transgenic mice overexpressing human amylo id precursor protein with the Swedish mutation to characterize this microgl ia response to amyloid deposits in aged mice. Analyses with MAC-1 and F4/80 antibodies as well as in vivo labeling with bromodeoxyuridine demonstrate that microglia in the plaque vicinity are in an activated state and that pr oliferation contributes to their accumulation at the plaque periphery. The amyloid-induced microglia activation may be mediated by scavenger receptor A, which is generally elevated, whereas the increased immunostaining of the receptor for advanced glycation end products is more restricted. Although components of the phagocytic machinery such as macrosialin and Fc receptors are increased in activated microglia, efficient clearance of amyloid is mi ssing seemingly because of the lack of amyloid-bound autoantibodies. Simila rly, although up-regulation of major histocompatibility complex class II (I A) points toward an intact antigen-presenting function of microglia, lack o f T and B lymphocytes does not indicate a cell-mediated immune response in the brains of APP23 mice. The similar characteristics of microglia in the A PP23 mice and in AD render the mouse model suitable to study the role of in flammatory processes during AD pathogenesis.