Early induction of interleukin-6 mRNA in the hippocampus and cortex of APPsw transgenic mice Tg2576

The neuropathological changes in Alzheimer's disease (AD) include the occur rence of activated microglia and astrocytes. Activated microglia expressing interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) immunoreactivity h ave been observed in close vicinity of the amyloid plaques in post-mortem t issue from AD patients. In order to further analyze the inflammatory proces s in relation to amyloidosis, we have studied the levels of markers for inf lammation in the brain of Tg(HuAPP695K670N/M671L)2576 transgenic mice (Tg25 76) that express high levels of human beta -amyloid precursor protein with the Swedish double mutation and develop prominent AD type neuropathology. T he mRNA levels for IL-1 beta, IL-1 beta -converting enzyme (ICE/caspase-1) and IL-6 were analyzed by semi-quantitative reverse transcription-polymeras e chain reaction in the cerebral cortex, hippocampus and cerebellum from Tg 2576 and wild type (wt) mice. The levels of mRNA for IL-1 beta and caspase- 1 were not significantly increased in either young (4 months) or aged (18 m onths) Tg2576 mice as compared to the age-matched wt mice. However, we obse rved an increase in IL-6 mRNA levels in the hippocampus and cortex of both 4- and 18-month-old transgenic mice as compared to wt mice. The increase in IL-6 mRNA levels in Tg2576 animals thus occurs before amyloid plaques can be detected (9-10 months). This would indicate that IL-6 mRNA induction is an early event in a beta -amyloid-induced immune response cascade or that i t may be involved in the amyloidosis. (C) 2001 Published by Elsevier Scienc e Ireland Ltd.