Objective

Dementia affects over 850,000 people in the UK and the cost to the economy is currently over £24 billion per annum. Alzheimer’s disease (AD) is the most common cause of dementia and one of the great health-care challenges of the 21st century. AD is an irreversible, progressive brain disease characterised by deposition of extracellular amyloid beta (Aβ) peptide and subsequent formation of neuritic plaques leading to dementia. There is no effective treatment for AD. Epidemiological studies report reduced prevalence of AD among users of nonsteroidal anti-inflammatory drugs (NSAIDs). The therapeutic effects of fenamate NSAIDs have been reported in a model of Aβ induced memory loss in transgenic mice. These data suggest that fenamates could be repurposed as NLRP3 inflammasome inhibitors and AD therapeutics. The aim of the current study was to investigate the hypothesis that fenamate NSAIDs prevent aggregation of Aβ1-42 peptide. The effects of mefenamic acid, flufenamic acid, ibuprofen and naproxen on Aβ1-42 aggregation were analysed spectrofluorometrically using the thioflavin-T assay and by gel electrophoresis, over 96 h.  Mefenamic acid was most effective at reducing Aβ1-42 aggregation. A reduction in the levels of intermediate sized (trimers/tetramers) Aβ1-42 peptide oligomers was consistently observed at an NSAID: Aβ1-42 peptide ratio of 20:1.