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. β-Amyloid (Aβ) 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 Aβ, with regard to release of the proinflammatory cytokines interleukin-1α (IL-1α), IL-1β, tumor necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ), as well as the IL-1 receptor antagonist (IL-1ra). Primary cultures of microglia from rat neonatal cerebral cortex were incubated with freshly dissolved Aβ_1-40 or Aβ_1-42, Aβ_1-40 fibrils, Aβ_1-40 βamy balls, or vehicle. Aβ_1-40 fibrils did not significantly stimulate any of these cytokines. Freshly dissolved Aβ_1-40 resulted in a marked increase in the release of IL-1β, and freshly dissolved Aβ_1-42 significantly stimulated both IL-1α and IFN-γ secretion. The Aβ_1-40 βamy balls stimulated the secretion of IL-1α and IL-1β. Incubation with Aβ peptides did not affect the secretion of IL-1ra, IL-6, or TNF-α. In the case of IL-1β, the response is correlated with the presence of Aβ peptide as monomers and oligomers.