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

Thomas, TomCA; Nadackal, T. George; Thomas, Kavita1

Neuropharmacology And Neurotoxicology

The neurotoxic and proinflammatory actions of the Alzheimer peptide amyloid-β (Aβ) are dependent on its aggregation and β-sheet conformation. Chronic use of non-steroidal anti-inflammatory 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 Aβ aggregation in vitro and reverse the β-sheet conformation of preformed fibrils at clinically relevant doses. Aspirin prevented enhanced Aβ 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.

Woodlands Medical Center and Endron Therapeutics, 3150 Tampa Road, #16 Oldsmar, FL 34677, USA 1Present Address: Department of Medicine, Orlando Regional Medical Center, Orlando, FL, USA

CACorresponding Author

Received 17 July 2001; accepted 8 August 2001

© 2001 Lippincott Williams & Wilkins, Inc.