Induction of cytokines in glial cells surrounding cortical β‐amyloid plaques in transgenic Tg2576 mice with Alzheimer pathology

Abstract

β‐Amyloid plaque deposition observed in brains from Alzheimer patients, might function as immune stimulus for glial/macrophages activation, which is supported by observations of activated microglia expressing interleukin (IL)‐1β and elevated IL‐6 immunoreactivity in close proximity to amyloid plaques. To elucidate the mechanisms involved in β‐amyloid‐mediated inflammation, transgenic mice (Tg2576) expressing high levels of the Swedish double mutation of human amyloid precursor protein and progressively developing typical β‐amyloid plaques in cortical brain regions including gliosis and astrocytosis, were examined for the expression pattern of a number of cytokines. Using ribonuclease protection assay, interleukin (IL)‐1α,‐β, IL‐1 receptor antagonist, IL‐6, IL‐10, IL‐12, IL‐18, interferon‐γ, and macrophage migration inhibitory factor (MIF) mRNA were not induced in a number of cortical areas of Tg2576 mice regardless of the postnatal ages studied ranging between 2 and 13 months. Using immunocytochemistry for IL‐1α,β, IL‐6, tumor necrosis factor (TNF)‐α, and macrophage chemotactic protein (MCP)‐1, only IL‐1β was found to be induced in reactive astrocytes surrounding β‐amyloid deposits detected in 14‐month‐old Tg2576 mice. Using non‐radioactive in situ hybridization glial fibrillary acidic protein (GFAP) mRNA was detected to be expressed by reactive astrocytes in close proximity to β‐amyloid plaques. The local immune response detected around cortical β‐amyloid deposits in transgenic Tg2576 mouse brain is seemingly different to that observed in brains from Alzheimer patients but may represent an initial event of chronic neuroinflammation at later stages of the disease.