Aspirin and non-steroidal anti-inflammatory drugs inhibit amyloid-β aggregation

The neurotoxic and proinflammatory actions of the Alzheimer peptide amyloid-beta (A beta) are dependent on its aggregation and beta -sheet conformation. Chronic use of non-steroidal antiinflammatory drugs (NSAIDs) such as aspirin for arthritis decreases the risk of developing Alzheimer's disease (AD) by unknown mechanisms. We report that these drugs inhibit human A beta aggregation in vitro and reverse the beta -sheet conformation of preformed fibrils at clinically relevant doses. Aspirin prevented enhanced A beta aggregation by aluminum, an environmental risk factor for AD. This anti-aggregatory effect was restricted to NSAIDs and was not exhibited by other drugs used in AD therapy. NSAIDS may have a role in the prevention and treatment of AD, in addition to a number of age-related disorders such as arthritis, cardiovascular disease and cancer. NeuroReport 12:3263-3267 (C) 2001 Lippincott Williams & Wilkins.