Lipid peroxidation and Alzheimer’s disease: Key role of Amyloid-β

INSERM Unité 551, Hôpital de la Pitié, Pavillon Benjamin Delessert, 83, Bd de l’Hôpital, 75651 Paris Cedex 13, France

^* kontush@chups.jussieu.fr

Abstract

Increased lipid peroxidation and elevated oxidative stress represent well-established characteristics of Alzheimer’s disease (AD). Amyloid-β (Aβ) peptide, a major component of amyloid plaques, can strongly influence oxidative processes. In aggregated form, Aβ has prooxidative properties, whereas in monomeric form it functions as an antioxidant. The antioxidative properties of monomeric Aβ are related to its ability to chelate transition metal ions, which are potent catalysts of oxidation. Aβ possesses an amphiphilic structure, associates with lipoproteins in vivo and may therefore function as a preventive antioxidant which protects lipoproteins from oxidation by transition metal ions. Increased production of Aβ in response to elevated oxidative stress has been documented in a number of in vitro studies, implying that production of monomeric Aβ as a lipoprotein antioxidant can be abnormally increased in response to elevated oxidative stress in aging. Subsequent accumulation of Aβ-metal aggregates, production of reactive oxygen species and toxic action to neuronal cells may represent a gain-of-function transformation and form temporal sequence of events in the development of AD.