β-amyloid protein structure determines the nature of cytokine release from rat microglia

Activated microglia represent a major source of inflammatory factors in Alzheimer's disease and a possible source of cytotoxic factors. beta-Amyloid (A beta) peptide, the predominant component in amyloid plaques, has been shown to activate microglia and stimulate their production of inflammatory factors. The present study was performed to analyze the responses of microglia to different forms of A beta, with regard to release of the proinflammatory cytokines interleukin-1 alpha: (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, and interferon-gamma (IFN-gamma), as well as the IL-1 receptor antagonist (IL-1ra). Primary cultures of microglia from rat neonatal cerebral cortex were incubated with freshly dissolved A beta(1-40) or A beta(1-42), A beta(1-40) fibrils, A beta(1-40) beta amy balls, or vehicle. A beta(1-40) fibrils, did not significantly stimulate any of these cytokines. Freshly dissolved A beta(1-40),, resulted in a marked increase in the release of IL-1 beta, and freshly dissolved A beta(1-42) significantly stimulated both IL-1 alpha and IFN-gamma secretion. The A beta(1-40) beta amy balls stimulated the secretion of IL-1a and IL-1 beta. Incubation with A beta peptides did not affect the secretion of IL-1ra, IL-6, or TNF-alpha. In the case of IL-1 beta, the response is correlated with the presence of A beta peptide as monomers and oligomers.