Characterisation of adducts of the lipid peroxidation product 4‐hydroxy‐2‐nonenal and amyloid β‐peptides by liquid chromatography/electrospray ionisation mass spectrometry

Alzheimer's disease is characterised by brain neuritic plaques composed of a 39–44 amino acid peptide (Aβ). Lipid peroxidation is an early event induced by these amyloid β-peptides, leading to the formation of 4-hydroxy-2-nonenal (HNE), which is one of the major end products of this process. HNE has been reported to form adducts via a stable covalent binding to proteins through a Michael addition to amino acid residues with a nucleophilic side chain. The present study reports an investigation of the conditions for formation of Aβ-HNE (Aβ 1–28 and Aβ 1–42) adducts, and their characterisation by liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS). The results suggest that one or more HNE moieties are localised in the 6–16 region of these adducts, while Asp-1, Lys-16 and Lys-28 are not modified under the described reaction conditions. Copyright © 2002 John Wiley & Sons, Ltd.