Patients on long-term non-steroidal anti-inflammatory drugs (NSAID) were seen to have a reduced risk of developing Alzheimer's disease, but the mechanisms underlying this observation remain unclear. But, in November 8 Nature, Sascha Weggen and colleagues from University of California, San Diego, La Jolla, California identify a subset of NSAIDs that have a direct action on the mechanism of amyloid production in the brain by reducing the 42-residue isoform of the amyloid-β peptide (Aβ42) levels independently of COX activity.