The elucidation of the intriguing relationship between oxidative stress and Alzheimer’s disease is crucial to understand
the pathogenesis of the disease as also to design a suitable drug trial with antioxidants against this condition. We
begin by reviewing the basic facts about Alzheimer’s disease and the chemistry and biology of oxygen free radicals with
particular reference to the cellular adaptive response through redox-signalling pathways. The post-mortem evidence of
oxidative damage in the brain of Alzheimer’s disease patients is overwhelming which is also supported by the similar
changes in transgenic mice models of this disease. However, the causal relationship of oxidative stress with amyloid beta
pathology or the genesis of Alzheimer’s disease is not clear. Considering the available evidence the review suggests that
the oxidative stress could be an early event in the disease process and may trigger various adaptive responses such as the
alterations of amyloid beta metabolism and the activation of stress responsive kinases which can subsequently lead to neuronal
degeneration and AD pathology. Further, we have presented a large body of evidence from various studies to highlight
the beneficial effects of antioxidants against amyloid beta toxicity or AD pathology in animal or cell based models of
AD. The failure of clinical trials with antioxidants against AD has been mentioned and the possible causes of such failures
have been analysed.
Keywords: Alzheimer’s disease, amyloid beta protein, oxidative stress, antioxidant, redox signalling, lipid peroxidation, protein
oxidation, DNA damage.
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