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


Address correspondence and reprint requests to Olivier Boutaud, PhD, Department of Pharmacology, Vanderbilt University, Nashville, TN, USA. E-mail:


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 β peptide. The product of the oxygenation of arachidonic acid by the cyclooxygenases, prostaglandin H2 (PGH2), rearranges non-enzymatically to several prostaglandins, including the highly reactive γ-keto aldehydes, levuglandins E2 and D2. We demonstrate that PGH2 markedly accelerates the formation of dimers and higher oligomers of amyloid β1−42. 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 β.