Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists modulate immunostimulated processing of APP through regulation of beta-secretase (BACE)

Prolonged intake of non-steroidal-anti-inflammatory drugs (NSAIDs) reduces the risk for Alzheimer's disease (AD). To determine the mechanisms by which inflammation affects AD and how NSAIDs protect against it, we stimulated N2a neuroblastoma cells stably transfected with amyloid precusor protein (APP) with pro-inflammatory cytokines, which increased the secretion of amyloid-beta (A-beta) and APP ectodomain. Addition of ibuprofen, indomethacin, peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists or cotransfection with PPARgamma cDNA reversed this effect. The inhibitory action of ibuprofen and in…