The DOI matches its Crossref record; 207 of the 207 references it cites were found in a registry or an index.
Oxidative stress hypothesis in Alzheimer’s disease
Abstract
The major hurdle in understanding Alzheimer's disease (AD) is a lack of knowledge about the etiology and pathogenesis of selective neuron death. In recent years, considerable data have accrued indicating that the brain in AD is under increased oxidative stress and this may have a role in the pathogenesis of neuron degeneration and death in this disorder. The direct evidence supporting increased oxidative stress in AD is: (1) increased brain Fe, Al, and Hg in AD, capable of stimulating free radical generation; (2) increased lipid peroxidation and decreased polyunsaturated fatty acids in the AD brain, and increased 4-hydroxynonenal, an aldehyde product of lipid peroxidation in AD ventricular fluid; (3) increased protein and DNA oxidation in the AD brain; (4) diminished energy metabolism and decreased cytochrome c oxidase in the brain in AD; (5) advanced glycation end products (AGE), malondialdehyde, carbonyls, peroxynitrite, heme oxygenase-1 and SOD-1 in neurofibrillary tangles and AGE, heme oxygenase-1, SOD-1 in senile plaques; and (6) studies showing that amyloid beta peptide is capable of generating free radicals. Supporting indirect evidence comes from a variety of in vitro studies showing that free radicals are capable of mediating neuron degeneration and death. Overall, these studies indicate that free radicals are possibly involved in the pathogenesis of neuron death in AD. Because tissue injury itself can induce reactive oxygen species (ROS) generation, it is not known whether this is a primary or secondary event. Even if free radical generation is secondary to other initiating causes, they are deleterious and part of a cascade of events that can lead to neuron death, suggesting that therapeutic efforts aimed at removal of ROS or prevention of their formation may be beneficial in AD.
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“In fact, a vast amount of evidence indicates that AD is perpetually accompanied by elevated oxidative cellular stress in the brain, yielded by the elevated production of free radicals, reduced polyunsaturated fatty acid, elevated protein and DNA oxidation, elevated lipid peroxidation, and the aggregation and accumulation of Aβ, which cause oxidative stress [28].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [28]
In the citing paper
“The oxidative stress hypothesis can be applied to other neurodegenerative diseases, such as Parkinson’s Disease (PD) and Amyotrophic Lateral Sclerosis (ALS) where the accumulation of oxidative damage over time leads to the late life onset and to the progressive nature of these diseases [29].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [29]
In the citing paper
“Decreased levels of phosphatidylcholine, phosphatidylethanolamine and the phospholipid precursors, choline and ethanolamine, have been described in AD and are considered specific for the pathogenic mechanism of AD. The depletion of phospholipids in AD has been referred to an increase of ROS-mediated lipid peroxidation [29].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [29]
In the citing paper
“All of these markers of OS have been described as an early alteration in the AD brain, and this concept has been used in the past to support the ‘oxidative stress hypothesis’ in the pathogenesis of AD [20,28,29,30].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [29]
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Metadata
- Authors
- Markesbery, W. R.
- Corresponding author
- Markesbery, William R.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 1997-01
- Volume
- 23
- Issue
- 1
- Pages
- 134-147
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2049192526
- Cited by
- 2,383
- References
- 207
- Citations by year
- 2026: 24 · 2025: 40 · 2024: 59 · 2023: 75 · 2022: 74 · 2021: 86 · 2020: 94 · 2019: 114 · 2018: 99 · 2017: 104 · 2016: 98 · 2015: 110 · 2014: 108 · 2013: 90 · 2012: 96
- FWCI
- 9.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P50AG005144, P01AG005119)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- Alzheimer's disease, oxidative stress, free radicals, reactive oxygen species, neuronal cell death, lipid peroxidation, 4-hydroxynonenal, protein oxidation, DNA oxidation, advanced glycation end products, heme oxygenase-1, superoxide dismutase 1, amyloid-beta, neurofibrillary tangles, amyloid plaques, energy metabolism, cytochrome c oxidase, metal ions
- MeSH terms
- Alzheimer Disease, Antioxidants, DNA Damage, Free Radicals, Humans, Neurons, Lipid Peroxidation, Amyloid beta-Peptides, Neurofibrillary Tangles, Cell Death, Oxidative Stress
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