Amyloid β-Peptide(1-42) Contributes to the Oxidative Stress and Neurodegeneration Found in Alzheimer Disease Brain

Authors

  • D. Allan Butterfield,

    Corresponding author
    1. Department of Chemistry, Center for Membrane Sciences, University of Kentucky, Lexington.
    2. Sanders-Brown Center on Aging, University of Kentucky, Lexington.
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  • Debra Boyd-Kimball

    1. Department of Chemistry, Center for Membrane Sciences, University of Kentucky, Lexington.
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Corresponding author: Professor D. Allan Butterfield, Department of Chemistry, Center for Membrane Sciences, and Sanders-Brown Center on Aging, 121 Chemistry-Physics Building, University of Kentucky, Lexington, KY 40506-0055 (E-mail: dabcns@uky.edu)

Abstract

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 Aβ1–42 from amyloid precursor protein are associated with an early onset and accelerated pathology of AD. Consequently, Aβ1–42 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 Aβ1–42 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 Aβ1–42.

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