Non-steroidal anti-inflammatory drugs have anti-amyloidogenic effects for Alzheimer's β-amyloid fibrils in vitro

The pathogenesis of Alzheimer's disease (AD) is characterized by cerebral deposits of amyloid β-peptides (Aβ) and neurofibrillary tangles which are surrounded by inflammatory cells. Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD and delays the onset of the disease. In the present study, we used fluorescence spectroscopy with thioflavin T and electron microscopy to examine the effects of NSAIDs such as ibuprofen, aspirin, meclofenamic acid sodium salt, diclofenac sodium salt, ketoprofen, flurbiprofen, naproxen, sulindac sulfide and indomethacin on the formation, extension, and destabilization of β-amyloid fibrils (fAβ) at pH 7.5 at 37 °C in vitro. All examined NSAIDs dose-dependently inhibited formation of fAβ from fresh Aβ(1-40) and Aβ(1-42), as well as their extension. Moreover, these NSAIDs dose-dependently destabilized preformed fAβs. The overall activity of the molecules examined was in the following order: ibuprofen ≈ sulindac sulfide ≥ meclofenamic acid sodium salt > aspirin ≈ ketoprofen ≥ flurbiprofen ≈ diclofenac sodium salt > naproxen ≈ indomethacin. Although the mechanisms by which these NSAIDs inhibit fAβ formation from Aβ, and destabilize preformed fAβ in vitro are still unclear, NSAIDs may be promising for the prevention and treatment of AD.