Heat shock protein-90-induced microglial clearance of exogenous amyloid-β1-42 in rat hippocampus in vivo

Alzheimer's disease is characterized by the accumulation of extracellular amyloid-P (Abeta) fibrils with microglia. In an in vitro microglial culture, we recently found that heat-shock protein-90 (Hsp90) enhanced the microglial phagocytosis and clearance of Abeta(1-42) (Abeta42). In this study, we examined the microinjection of Abeta42 in the presence or absence of Hsp90 into the rat hippocampus in vivo. Intrahippocampal injection of Abeta42 alone induced microglial accumulation, and the amount of Abeta42 then gradually decreased. In addition, simultaneous injection with Hsp90 significantly reduced the amount of Abeta42 and increased the production of cytokines. These results suggest that Hsp90 may facilitate microglial Abeta42 clearance in rat brain in vivo. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.