Prostaglandin H2 (PGH2) accelerates formation of amyloid β1-42 oligomers

Epidemiologic evidence implicates cyclooxygenase activity in the pathogenesis of Alzheimer's disease, in which amyloid plaques have been found to contain increased levels of dimers and higher multimers of the amyloid beta peptide. The product of the oxygenation of arachidonic acid by the cyclooxygenases, prostaglandin H-2 (PGH(2) ), rearranges non-enzymatically to several prostaglandins, including the highly reactive gamma-keto aldehydes, levuglandins E-2 and D-2 . We demonstrate that PGH(2) markedly accelerates the formation of dimers and higher oligomers of amyloid beta(1-42) . This is associated with the formation of levuglandin adducts of the peptide. These findings provide the molecular basis for a hypothesis linking cyclooxygenase activity to the formation of oligomers of amyloid beta.