P4–286: Secretion of the soluble APP ectodomain (APPS) is not affected by the non–steroidal anti–inflammatory drugs ibuprofen and indomethacin in primary neuronal cultures

Nonsteroidal Anti-Inflammatory Drugs and Ectodomain Shedding of the Amyloid Precursor Protein

<i>Background:</i> Epidemiological studies have suggested that long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer’s disease (AD). Several mechanisms have been proposed to explain these findings including increased shedding of the soluble ectodomain of the amyloid precursor protein (sAPP), which functions as a neurotrophic and neuroprotective factor in vitroand in vivo. <i>Objective:</i> To clarify whether NSAIDs consistently stimulate sAPP secretion. <i>Methods:</i> 293-EBNA cells with stable overexpression of an APP-alkaline phosphatase fusion protein (APP-AP), SH-SY5Y and PC12 cells or prim…