title: Role of by-products of lipid oxidation in Alzheimer's disease brain: a focus on acrolein.
abstract: Abundant data consistently support the idea that oxidative stress occurs and is a constant feature of Alzheimer's disease (AD). Some recent evidence indicated that phenomenon is an early event and might be implicated in the pathogenesis of this disease. Lipid peroxidation leads to the formation of a number of aldehydes by-products, including malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), and acrolein. The most abundant aldehydes are HNE and MDA while acrolein is the most reactive. Increased levels of specific HNE-histidine and glutathione-HNE Michael adducts in AD brain has been reported. Proteomic analysis demonstrated a large number of protein-bound HNE in AD brain. F2-isoprostanes (F2-IsoPs) levels and neuroprostanes were also significantly increased in mild cognitive impairment (MCI) patients and in late-stage AD. In brain from patients with AD, acrolein has been found to be elevated in hippocampus and temporal cortex where oxidative stress is high. Due to its high reactivity, acrolein is not only a marker of lipid peroxidation but also an initiator of oxidative stress by adducting cellular nucleophilic groups found on proteins, lipids, and nucleic acids. Interestingly, data indicates that lipid peroxidation occurs in the brain of MCI and also in preclinical AD patients suggesting that oxidative damage may play an early role in the pathogenesis of AD. In this review, we will summarize some mechanisms implicated in the toxicity of by-products of lipid peroxidation such as IsoPs, HNE, and acrolein and their implication in AD.
authors.affiliation: INRS-Institut Armand-Frappier, Laval, PQ, Canada.
authors.forename: Manjeet
authors.initials: M
authors.lastname: Singh
authors.forename: Thanh Nam
authors.initials: TN
authors.lastname: Dang
authors.forename: Madeleine
authors.initials: M
authors.lastname: Arseneault
authors.forename: Charles
authors.initials: C
authors.lastname: Ramassamy
mesh_terms: D000171:Acrolein / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015227:Lipid Peroxidation; D018384:Oxidative Stress
chemical_list: D000171:Acrolein