Amyloid β-peptide(1-42) contributes to the oxidative stress and neurodegeneration found in Alzheimer disease brain

Oxidative stress is extensive in Alzheimer disease (AD) brain. Amyloid β-peptide (1-42) has been shown to induce oxidative stress and neurotoxicity in vitro and in vivo. Genetic mutations that result in increased production of Aβ_1-42 from amyloid precursor protein are associated with an early onset and accelerated pathology of AD. Consequently, Aβ_1-42 has been proposed to play a central role in the pathogenesis of AD as a mediator of oxidative stress. In this review, we discuss the role of Aβ_1-42 in the lipid peroxidation and protein oxidation evident in AD brain and the implications of such oxidative stress for the function of various proteins that we have identified as specifically oxidized in AD brain compared to control, using proteomics methods. Additionally, we discuss the critical role of methionine 35 in the oxidative stress and neurotoxic properties exhibited by Aβ_1-42.