Mehlhorn Gaby. Hollborn Margrit. Schliebs Reinhard.
Induction of cytokines in glial cells surrounding cortical beta-amyloid
plaques in transgenic Tg2576 mice with Alzheimer pathology, International Journal of Developmental Neuroscience 18(4-5) :423-431, 2000.
Abstract
beta-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)-1beta and elevated IL-6 immunoreactivity in close proximity to amyloid
plaques. To elucidate the mechanisms involved in beta-amyloid-mediated
inflammation, transgenic mice (Tg2576) expressing high levels of the Swedish
double mutation of human amyloid precursor protein and progressively
developing typical beta-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)-1alpha,-beta, IL-1 receptor antagonist, IL-6, IL-10, IL-12, IL-18,
interferon-gamma, 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-1alpha,beta, IL-6, tumor necrosis factor
(TNF)-alpha, and macrophage chemotactic protein (MCP)-1, only IL-1beta was
found to be induced in reactive astrocytes surrounding beta-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 beta-amyloid plaques.
The local immune response detected around cortical beta-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.
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