NSAIDs tackle Alzheimer's disease

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.

Weggen et al. found that ibuprofen, indomethacin and sulindac sulphide decrease the highly amyloidogenic Aβ42 peptide produced by cultured cells and mutant mice. This effect was not seen in other NSAIDs suggesting a process that is independent of COX inhibition. Because non-amyloidogenic Aβ(1–38) isoform was increased, the authors suggest that NSAIDs alter γ-secretase activity without perturbing other β-amyloid precursor protein processing pathways (Nature 2001, 414:212-216).

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