Microglia activation mediates fibrillar amyloid-β toxicity in the aged primate cortex.

ABSTRACT: The amyloid-β peptide (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD). The fibrillar form of Aβ (fAβ) exerts toxic effects on neurons through mechanisms not well understood. We have shown that the aged primate cortex is selectively vulnerable to fAβ toxicity at low concentrations. In addition to neuronal loss, fAβ induced massive activation of microglia in the aged rhesus cortex. We now demonstrate that inhibition of microglia activation abolishes fAβ toxicity. Injection or pump delivery of macrophage/microglia inhibitory factor (MIF) significantly reduced activation of microglia and the volume of damage caused by fAβ. Microglia isolated from aged rhesus cortex produced substantial reactive oxygen species when stimulated by fAβ, which was inhibited by MIF in a dos

SUBMITTER: Leung E 

PROVIDER: S-EPMC2888944 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature