Prostaglandin H2‐derived adducts of proteins correlate with Alzheimer's disease severity

The formation of cyclooxygenase‐derived lipid adducts of protein in brains of patients who had Alzheimer's disease has been investigated. The enzymatic product of the cyclooxygenases, prostaglandin H2, rearranges in part to highly reactive γ‐ketoaldehydes, levuglandin (LG) E2 and LGD2. These γ‐ketoaldehydes react with free amines on proteins to yield a covalent adduct. Utilizing analysis of the levuglandinyl‐lysine adducts by liquid chromatography‐tandem mass spectrometry, we now find that this post‐translational modification is increased significantly in the hippocampus in Alzheimer's disease. The magnitude of the increase correlates with the pathological evidence of severity.