Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid β-peptide
Abstract
Amyloid beta-peptide (Abeta) is heavily deposited in the brains of Alzheimer's disease (AD) patients. Free-radical oxidative stress, particularly of neuronal lipids, proteins and DNA, is extensive in those AD brain areas in which Abeta is abundant. Recent research suggests that these observations might be linked, and it is postulated that Abeta-induced oxidative stress leads to neurodegeneration in AD brain. Consonant with this postulate, Abeta leads to neuronal lipid peroxidation, protein oxidation and DNA oxidation by means that are inhibited by free-radical antioxidants. Here, we summarize current research on phospholipid peroxidation, as well as protein and DNA oxidation, in AD brain, and discuss the potential role of Abeta in this oxidative stress.
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Oxidative and nitrosative stress are critical factors in the pathogenesis and progression of Alzheimer disease and amnestic mild cognitive impairment.
“Oxidative and nitrosative stress are widely recognized as critical factors in the pathogenesis and progression of Alzheimer disease (AD) and its earlier stage, amnestic mild cognitive impairment (MCI).”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [9]
Aβ42 oligomers cause oxidative damage.
“Aβ42 oligomers cause oxidative damage as mentioned above”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [9]
Aβ42 oligomers lead to synaptic dysfunction correlated with cognitive loss.
“and these oligomers also lead to synaptic dysfunction correlated with cognitive loss [8,9,26].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [9]
Brains of patients with AD exhibit prominent hallmarks of oxidative damage and decreased PRDX1 acetylation and thiol-reductive activity.
“Brains of patients with AD exhibit prominent hallmarks of oxidative damage and decreased PRDX1 acetylation and thiol-reductive activity (47, 48) that could collectively impair GDE2 trafficking and function.”
From GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein (2021) · cites this paper as [47]
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Butterfield, D. A., Di Domenico, F., & Barone, E. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.06.010 · Cited by 402 · see citing works
Self-citationButterfield, D. A., & Boyd-Kimball, D. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-170543 · Cited by 403 · see citing works
Self-citationReddy, P. H., Tripathi, R., Troung, Q., Tirumala, K., Reddy, T. P., Anekonda, V., Shirendeb, U. P., Calkins, M. J., Reddy, A. P., Mao, P., et al. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.011 · Cited by 394 · see citing works
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Self-citationDrake, J. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00225-7 · Cited by 371 · see citing works
Self-citationIdentification of nitrated proteins in Alzheimer’s disease brain using a redox proteomics approach
Sultana, R., Poon, H. F., Cai, J., Pierce, W. M., Merchant, M., Klein, J. B., Markesbery, W. R., & Butterfield, D. A. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.10.004 · Cited by 364 · see citing works
Self-citationTramutola, A., Triplett, J. C., Di Domenico, F., Niedowicz, D. M., Murphy, M. P., Coccia, R., Perluigi, M., & Butterfield, D. A. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13037 · Cited by 347 · see citing works
Self-citationOxidative Stress Signaling in Alzheimers Disease
Su, B., Wang, X., Nunomura, A., Moreira, P., Lee, H.-G., Perry, G., Smith, M., & Zhu, X. (2008) · Current Alzheimer Research · doi:10.2174/156720508786898451 · Cited by 344 · see citing works
Causes of oxidative stress in Alzheimer disease
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Oxidative stress, protein modification and Alzheimer disease
Tramutola, A., Lanzillotta, C., Perluigi, M., & Butterfield, D. A. (2017) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.06.005 · Cited by 303 · see citing works
Self-citationZinc homeostasis and neurodegenerative disorders
Szewczyk, B. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00033 · Cited by 288 · see citing works
Jaeger, L. B., Dohgu, S., Sultana, R., Lynch, J. L., Owen, J. B., Erickson, M. A., Shah, G. N., Price, T. O., Fleegal-Demotta, M. A., Butterfiled, D. A., et al. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.01.017 · Cited by 281 · see citing works
Reed, T., Perluigi, M., Sultana, R., Pierce, W. M., Klein, J. B., Turner, D. M., Coccia, R., Markesbery, W. R., & Butterfield, D. A. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.12.007 · Cited by 257 · see citing works
Self-citationDi Domenico, F., Tramutola, A., & Butterfield, D. A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.10.490 · Cited by 253 · see citing works
Self-citationEsposito, L., Raber, J., Kekonius, L., Yan, F., Yu, G.-Q., Bien-Ly, N., Puoliväli, J., Scearce-Levie, K., Masliah, E., & Mucke, L. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0482-06.2006 · Cited by 254 · see citing works
Liu, Q., Xi, Y., Wang, Q., Liu, J., Li, P., Meng, X., Liu, K., Chen, W., Liu, X., & Liu, Z. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.04.005 · Cited by 241 · see citing works
Early neuronal accumulation of DNA double strand breaks in Alzheimer’s disease
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Nitric oxide and nitroxidative stress in Alzheimer's disease
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Opii, W. O., Joshi, G., Head, E., Milgram, N. W., Muggenburg, B. A., Klein, J. B., Pierce, W. M., Cotman, C. W., & Butterfield, D. A. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.09.012 · Cited by 202 · see citing works
Self-citationReed, T. T., Pierce, W. M., Markesbery, W. R., & Butterfield, D. A. (2009) · Brain Research · doi:10.1016/j.brainres.2009.04.009 · Cited by 190 · see citing works
The effects of dietary restriction on oxidative stress in rodents
Walsh, M. E., Shi, Y., & Van Remmen, H. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.05.037 · Cited by 181 · see citing works
Turunc Bayrakdar, E., Uyanikgil, Y., Kanit, L., Koylu, E., & Yalcin, A. (2014) · Free Radical Research · doi:10.3109/10715762.2013.857018 · Cited by 169 · see citing works
Glycation—a sweet tempter for neuronal death
Kikuchi, S. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(02)00273-4 · Cited by 169 · see citing works
Interaction of Mitochondrial Calcium and ROS in Neurodegeneration
Baev, A. Y., Vinokurov, A. Y., Novikova, I. N., Dremin, V. V., Potapova, E. V., & Abramov, A. Y. (2022) · Cells · doi:10.3390/cells11040706 · Cited by 162 · see citing works
Can herbs provide a new generation of drugs for treating Alzheimer’s disease?
Anekonda, T. S., & Reddy, P. H. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.09.001 · Cited by 140 · see citing works
Barone, E., Di Domenico, F., Mancuso, C., & Butterfield, D. A. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.09.018 · Cited by 127 · see citing works
Self-citationButterfield, D. A. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.06.006 · Cited by 126 · see citing works
Self-citationNitric Oxide: Exploring the Contextual Link with Alzheimer’s Disease
Asiimwe, N., Yeo, S. G., Kim, M.-S., Jung, J., & Jeong, N. Y. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/7205747 · Cited by 125 · see citing works
Genome instability in Alzheimer disease
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Methionine-35 of A <i>β</i> (1–42): Importance for Oxidative Stress in Alzheimer Disease
Butterfield, D. A., & Sultana, R. (2011) · Journal of Amino Acids · doi:10.4061/2011/198430 · Cited by 124 · see citing works
Self-citationCirculating Biomarkers of Cognitive Decline and Dementia
Solfrizzi, V., D'Introno, A., Colacicco, A. M., Capurso, C., Todarello, O., Pellicani, V., Capurso, S. A., Pietrarossa, G., Santamato, V., Capurso, A., et al. (2006) · Clinica Chimica Acta · doi:10.1016/j.cca.2005.06.015 · Cited by 120 · see citing works
Oxidative modification of lipoic acid by HNE in Alzheimer disease brain
Hardas, S. S., Sultana, R., Clark, A. M., Beckett, T. L., Szweda, L. I., Murphy, M. P., & Butterfield, D. A. (2013) · Redox Biology · doi:10.1016/j.redox.2013.01.002 · Cited by 120 · see citing works
Self-citationYoung, M. L., & Franklin, J. L. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.103409 · Cited by 120 · see citing works
Di Domenico, F., Barone, E., Perluigi, M., & Butterfield, D. A. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6759 · Cited by 114 · see citing works
Self-citationRedox proteomics and amyloid β-peptide: Insights into Alzheimer disease
Butterfield, D. A., & Boyd‐Kimball, D. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14589 · Cited by 105 · see citing works
Self-citationBoyd-Kimball, D., Poon, H. F., Lynn, B. C., Cai, J., Pierce Jr., W. M., Klein, J. B., Ferguson, J., Link, C. D., & Butterfield, D. A. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.07.001 · Cited by 98 · see citing works
Cognitive impairment in humanized APP×PS1 mice is linked to Aβ1–42 and NOX activation
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Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease
Butterfield, D. A., & Boyd-Kimball, D. (2020) · Antioxidants · doi:10.3390/antiox9090818 · Cited by 85 · see citing works
“Aβ42 oligomers cause oxidative damage as mentioned above, and these oligomers also lead to synaptic dysfunction correlated with cognitive loss [8,9,26].”
BackgroundSelf-citationPhloroglucinol Attenuates the Cognitive Deficits of the 5XFAD Mouse Model of Alzheimer’s Disease
Yang, E.-J., Ahn, S., Ryu, J., Choi, M.-S., Choi, S., Chong, Y. H., Hyun, J.-W., Chang, M.-J., & Kim, H.-S. (2015) · PLOS ONE · doi:10.1371/journal.pone.0135686 · Cited by 87 · see citing works
Butterfield, D. A., Barone, E., & Mancuso, C. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2011.04.007 · Cited by 80 · see citing works
“Of course, oxidative stress is strongly associated with amnestic MCI and AD [94–96], and Aβ is hypothesized to contribute to this oxidative stress [97].”
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Cenini, G., Sultana, R., Memo, M., & Butterfield, D. A. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.03.015 · Cited by 79 · see citing works
Self-citationLiu, Y., Chen, Z., Li, B., Yao, H., Zarka, M., Welch, J., Sachdev, P., Bridge, W., & Braidy, N. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2020.104931 · Cited by 69 · see citing works
Oxidative stress damage and oxidative stress responses in the choroid plexus in Alzheimer’s disease
Perez-Gracia, E., Blanco, R., Carmona, M., Carro, E., & Ferrer, I. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0574-4 · Cited by 63 · see citing works
Iron Pathophysiology in Alzheimer’s Diseases
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Self-citationSultana, R., Newman, S. F., Abdul, H. M., Cai, J., Pierce, W. M., Klein, J. B., Merchant, M., & Butterfield, D. A. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20876 · Cited by 53 · see citing works
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GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein
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Some evolutionary perspectives on Alzheimer's disease pathogenesis and pathology
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Do Microglia default on network maintenance in Alzheimer's disease?
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Self-citationSupasitthumrong, T., Tunvirachaisakul, C., Aniwattanapong, D., Tangwongchai, S., Chuchuen, P., Tawankanjanachot, I., Snabboon, T., Hemrungrojn, S., Carvalho, A. F., & Maes, M. (2019) · Journal of Alzheimer’s Disease · doi:10.3233/jad-190114 · Cited by 13 · see citing works
- Authors
- Butterfield, D. A., Drake, J., Pocernich, C., & Castegna, A.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Butterfield, D.Allan
- Venue
- Trends in Molecular Medicine
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 7
- Issue
- 12
- Pages
- 548-554
- ISSN
- 1471-4914 (ISSN-L)
- OpenAlex
- W1986384924
- Cited by
- 1,114
- References
- 77
- Citations by year
- 2026: 6 · 2025: 27 · 2024: 31 · 2023: 28 · 2022: 28 · 2021: 47 · 2020: 49 · 2019: 54 · 2018: 43 · 2017: 55 · 2016: 53 · 2015: 53 · 2014: 79 · 2013: 54 · 2012: 43
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- National Institute on Aging (P01AG010836, P01AG005119, AG 10836, AG12423, AG0 5119, R01AG012423)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta, oxidative stress, lipid peroxidation, phospholipid peroxidation, protein oxidation, DNA oxidation, free radicals, antioxidants, neurodegeneration, brain
- MeSH terms
- Alzheimer Disease, Brain, DNA, Free Radicals, Humans, Nerve Tissue Proteins, RNA, Lipid Peroxidation, Amyloid beta-Peptides, Oxidative Stress
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