INTELEUKIN-10 INDUCES METABOLIC CHANGES DRIVING Aβ IMMUNE TOLERANCE IN MACROPHAGES

Abstract

over pathological progression in the hippocampus of APP/ PS1dE9 transgenic mice. Methods: Cyclosporine (15 mg/kg) and prednisone (20 mg/kg) were intraperitoneally administered to 9 month-old APP/PS1dE9 mice for 3 months. Untreated mice were used as controls. Hippocampal amyloid burden, microglial and astroglial response, cytokines production, tau phosphorylation and neurodegeneration were assessed by immunohistochemistry and molecular techniques (Western-blot and RT-qPCR). Results: The microglial marker Iba1 and some proinflammatory cytokines were found to be decreased by RT-qPCR in immunosuppressed mice compared to controls. Conversely, a significant increase in total Ab levels and the astroglial marker GFAP was detected. Moreover, the treatment exacerbated GABAergic interneuronal (Somatostatin and Neuropeptide Y-positive) degeneration. Conclusions: Immunosuppression treatment downregulated microglial population activity and accelerated not only amyloid pathology but also the neuronal degeneration in this APP/PS1 model. Deficiencies in the innate immune system with age could promote AD pathology and cognitive decline in patients. Therefore, regulating microglial activation signalling pathways might be considered as a therapeutic target for AD. Supported by PI15/00796 and PI18/01557 (to AG), PI15/00957 and PI18/1556 (to JV), and Ciberned (to AG and JV).