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.