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 occurrence of activated microglia and astrocytes. Activated microglia expressing interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) immunoreactivity have been observed in close vicinity of the amyloid plaques in post-mortem tissue from AD patients. In order to further analyze the inflammatory process in relation to amyloidosis, we have studied the levels of markers for inflammation in the brain of Tg(HuAPP695K670N/M671L)2576 transgenic mice (Tg2576) that express high levels of human beta-amyloid precursor protein with the Swedish double mutation and develop prominent AD type neuropathology. The mRNA levels for IL-1beta, IL-1beta-converting enzyme (ICE/caspase-1) and IL-6 were analyzed by semi-quantitative reverse transcription-polymerase chain reaction in the cerebral cortex, hippocampus and cerebellum from Tg2576 and wild type (wt) mice. The levels of mRNA for IL-1beta and caspase-1 were not significantly increased in either young (4 months) or aged (18 months) Tg2576 mice as compared to the age-matched wt mice. However, we observed 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 it may be involved in the amyloidosis.