ENHANCED PROCESSING OF APP INDUCED BY IL-1-BETA CAN BE REDUCED BY INDOMETHACIN AND NORDIHYDROGUAIARETIC ACID

Abnormal processing of the amyloid precursor protein (APP) is thought to contribute to the formation of amyloid plaques in Alzheimer's disea se. Several studies suggest that inflammation, and possibly the cytoki nes released during the inflammatory process, may participate in the p laque formation. We have utilized a cell culture system to examine the effects of the cytokine interleukin-1 beta (IL-1 beta) on the process ing of APP. We present data to show that IL-1 beta increases the matur ation of APP and causes enhanced processing of the full length APP iso forms. In addition, as reported previously in HUVEC cells, IL-1 beta i ncreases the secretion of APP in PC12 cells. Indomethacin and NDGA, re ported inhibitors of the cyclooxygenase and lipoxygenase pathways, res pectively, block these effects,suggesting the involvement of prostagla ndins and leukotrienes in IL-1 beta mediated APP processing. (C) 1995 Academic Press, Inc.