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

beta-Amyloid plaque deposition observed in brains from Alzheimer patients, might function as immune stimulus for glial/macrophages activation, which i s supported by observations of activated microglia expressing interleukin ( IL)-1 beta and elevated IL-6 immunoreactivity in close proximity to amyloid plaques. To elucidate the mechanisms involved in beta-amyloid-mediated inf lammation, transgenic mice (Tg2576) expressing high levels of the Swedish d ouble mutation of human amyloid precursor protein and progressively develop ing typical P-amyloid plaques in cortical brain regions including gliosis a nd astrocytosis; were examined for the expression pattern of a number of cy tokines. Using ribonuclease protection assay, interleukin (IL)-1 alpha,-beta, IL-1 r eceptor antagonist, IL-6, IL-10, IL-12, IL-18, interferon-gamma, and macrop hage migration inhibitory factor (MIF) mRNA were not induced in a number of cortical areas of Tg2576 mice regardless of the postnatal ages studied ran ging between 2 and 13 months. Using immunocytochemistry for IL-1 alpha,beta , IL-6, tumor necrosis factor (TNF)-alpha, and macrophage chemotactic prote in (MCP)-1, only IL-1 beta was found to be induced in reactive astrocytes s urrounding beta-amyloid deposits detected in 14-month-old Tg2576 mice. Usin g non-radioactive in situ hybridization glial fibrillary acidic protein (GF AP) mRNA was detected to be expressed by reactive astrocytes in close proxi mity to beta-amyloid plaques. The local immune response detected around cor tical beta-amyloid deposits in transgenic Tg2576 mouse brain is seemingly d ifferent to that observed in brains from Alzheimer patients but may represe nt an initial event of chronic neuroinflammation at later stages of the dis ease. (C) 2000 ISDN. Published by Elsevier Science Ltd. All rights reserved .