Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro

We have previously developed and characterized isolated microglia and astro cyte cultures from rapid (<4 h) brain autopsies of Alzheimer's disease (AD) and nondemented elderly control (ND) patients. In the present study, we ev aluate the inflammatory repertoire of AD and ND microglia cultured from whi te matter (corpus callosum) and gray matter (superior frontal gyrus) with r espect to three major proinflammatory cytokines, three chemokines, a classi cal pathway complement component, a scavenger cell growth factor, and a rea ctive nitrogen intermediate. Significant, dose-dependent increases in the p roduction of pro-interleukin-1<beta> (pro-IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein- 1 (MCP-1), macrophage inflammatory peptide-1 alpha (MIP-1 alpha), IL-8, and macrophage colony-stimulating factor (M-CSF) were observed after exposure to pre-aggregated amyloid beta peptide (1-42) (A beta1-42). Across constitu tive and A beta -stimulated conditions, secretion of complement component C 1q, a reactive nitrogen intermediate, and M-CSF was significantly higher in AD compared with ND microglia. Taken together with previous in situ hybrid ization findings, these results demonstrate unequivocally that elderly huma n microglia provide a brain endogenous source for a wide range of inflammat ory mediators. GLIA 35:72-79, 2001. (C) 2001 Wiley-Liss, Inc.