Methionine 35 oxidation reduces fibril assembly of the amyloid aβ-(1-42) peptide of Alzheimer's disease

Abstract

The major component of amyloid plaques in Alzheimer's disease (AD) is Aβ, a small peptide that has high propensity to assemble as aggregated β-sheet structures. Using three well established techniques for studying amyloid structure, namely circular dichroism, thioflavin-T fluorescence, and atomic force microscopy, we demonstrate that oxidation of the Met-35 side chain to a methionine sulfoxide (Met-35ox) significantly hinders the rate of fibril formation for the 42-residue Aβ-(1-42) at physiological pH. Met-35ox also alters the characteristic Aβ fibril morphology and prevents formation of the protofibril, which is a key intermediate in β-amyloidosis and the associated neurotoxicity. The implications of these results for the biological function and role of Aβ with oxidative stress in AD are discussed.