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Oxidative Stress and Alzheimer’s Disease

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Inflammation, Aging, and Oxidative Stress

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that causes dementia in the elderly. AD is the leading cause of senile dementia and although the pathogenesis of this disorder is not fully understood, various hypotheses have been developed based on experimental data accumulated since the initial description of this disease by Alois Alzheimer about 90 years ago. Most approaches to explaining the pathogenesis of AD focus on its two histopathological hallmarks: amyloid β protein (Aβ) -loaded senile plaques and neurofibrillary tangles, which consist of the filament protein tau. Growing evidence reveals that oxidative stress is an important factor contributing to the initiation and progression of AD. Oxidative stress, manifested by protein oxidation, lipid peroxidation, DNA oxidation, and 3-nitrotyrosine formation, among other indices, is observed in AD brain. However, the mechanisms that lead to the disruption of redox balance and the sources of free radicals remain elusive. The excessive reactive oxygen species may be generated from mechanisms such as mitochondria dysfunction and/or aberrant accumulation of transition metals, while the abnormal accumulation of Aβ and tau proteins appears to promote the redox imbalance. The resultant oxidative stress has been implicated in Aβ- or tau-induced neurotoxicity. In addition, evidence has suggested that oxidative stress may augment the production and aggregation of Aβ and facilitate the phosphorylation and polymerization of tau, thus forming a vicious cycle that promotes the initiation and progression of AD.

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Acknowledgements

Support provided by the Semmes Foundation and by a grant from the National Institute on Minority Health and Health Disparities (G12MD007591) from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, UP, 221 005, India

    Sandeep Kumar Singh

  2. Department of Pathology, School of Medicine, University of Maryland, Baltimore, MD, USA

    Rudy Castellani

  3. College of Sciences, The University of Texas at San Antonio, One UTSA Circle, San Antonio, TX, 78249, USA

    George Perry Ph.D.

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  1. Sandeep Kumar Singh
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  2. Rudy Castellani
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  3. George Perry Ph.D.
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Correspondence to George Perry Ph.D. .

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Editors and Affiliations

  1. Department of Medicine, Center for Occupational and Environmental Health, University of California, Irvine, California, USA

    Stephen C. Bondy

  2. Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, California, USA

    Arezoo Campbell

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Singh, S.K., Castellani, R., Perry, G. (2016). Oxidative Stress and Alzheimer’s Disease. In: Bondy, S., Campbell, A. (eds) Inflammation, Aging, and Oxidative Stress. Oxidative Stress in Applied Basic Research and Clinical Practice. Springer, Cham. https://doi.org/10.1007/978-3-319-33486-8_10

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