beta-Amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology

To elucidate the mechanisms involved in beta -amyloid-mediated inflammation in Alzheimer's disease, transgenic Tg2576 mice containing as transgene the Swedish double mutation of human amyloid precursor protein 695, were exami ned for the expression pattern of various cytokines using double immunocyto chemistry and laser scanning microscopy. Tg2576 mice studied at postnatal a ges of 13, 16 and 19 months demonstrated an age-related accumulation of bot h senile and diffuse beta -amyloid plaques in neocortex and hippocampus. Re active interleukin (IL)-1 beta -immunoreactive astrocytes were found in clo se proximity to both fibrillary and diffuse beta -amyloid deposits detectab le at very early stages of plaque development, while activated microglia ap peared in acid around fibrillary beta -amyloid plaques only. Subpopulations of reactive astrocytes also demonstrated immunolabeling for transforming g rowth factor (TGF)-beta1, TGF-beta3, and IL-IO, already detectable in 13-mo nth-old transgenic mouse brain, while a few IL-6-immunoreactive astrocytes were observed only at later stages of plaque development. The early beta -a myloid-mediated upregulation of IL-1 beta, TGF-beta, and IL-10 in surroundi ng reactive astrocytes indicates the induction of both pro- and anti-inflam matory mechanisms. The transgenic approach used in this study may thus prov ide a useful tool to further disclose the in vivo mechanisms by which pro- and anti-inflammatory cytokines interact and/or contribute to the progressi on of Alzheimer's disease. (C) 2001 Elsevier Science B.V. All rights reserv ed.