Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the treatment of rheumatoid arthritis. NSAID users have previously been shown to have a reduced risk of developing Alzheimer's disease. The deposition of the 42-residue isomer of the amyloid-? peptide (A?42) is central to the pathogenesis of Alzheimer's disease. A?42 is generated by cleavage of the amyloid precursor protein (APP) by a ?-secretase that cleaves APP at different positions thereby generating peptides of different lengths. This study investigates the mechanism through which NSAIDs exert their protective effect against the development of Alzheimer's disease.