Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease
Open accessAbstract
Alzheimer disease (AD) is a neurodegenerative disease which is characterized by the presence of extracellular senile plaques mainly composed of amyloid-beta peptide (Abeta), intracellular neurofibrillary tangles, and selective synaptic and neuronal loss. AD brains revealed elevated levels of oxidative stress markers which have been implicated in Abeta-induced toxicity. In the present work we addressed the hypothesis that oxidative stress occurs early in the development of AD and evaluated the extension of the oxidative stress and the levels of antioxidants in an in vivo model of AD, the triple-transgenic mouse, which develops plaques, tangles, and cognitive impairments and thus mimics AD progression in humans. We have shown that in this model, levels of antioxidants, namely, reduced glutathione and vitamin E, are decreased and the extent of lipid peroxidation is increased. We have also observed increased activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. These alterations are evident during the Abeta oligomerization period, before the appearance of Abeta plaques and neurofibrillary tangles, supporting the view that oxidative stress occurs early in the development of the disease.
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Aβ deposition and early cognitive impairment are preceded by mitochondrial dysfunction and increased oxidative stress in 3xTg-AD mouse brains.
“Aβ deposition and early cognitive impairment are preceded by mitochondrial dysfunction and increased oxidative stress in 3xTg-AD mouse brains (Resende et al., 2008; Yao et al., 2009).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Resende et al., 2008
The Discussion reports increased lipid peroxidation in 3- to 5-month-old 3×Tg-AD mice before Aβ plaque deposition, supporting the early oxidative-stress portion of the claim. It does not establish mitochondrial dysfunction in those mice or show that either change precedes early cognitive impairment. Page numbers are not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe earliest pathological changes in 3xTg-AD mice involve mitochondrial impairment and increased oxidative stress.
“Notably, the earliest pathological changes in 3xTg-AD mice involve mitochondrial impairment and increased oxidative stress (Resende et al., 2008; Yao et al., 2009).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Resende et al., 2008
The Results and Discussion report increased oxidative stress in 3–5-month-old 3×Tg-AD mice before plaques and tangles appear. They do not establish mitochondrial impairment as an early change in these mice; the Discussion’s mention of mitochondrial vulnerability concerns a different tau-transgenic model. (LLM, conf=0.88)
Experimental — accuracy not yet measuredResende et al. (2008) reported that several markers for oxidative stress were higher in the brains of 3- to 5-month-old 3xTg-AD mice than in nonTg mice of the same age.
“Resende et al. (2008) reported that several markers for oxidative stress were higher in the brains of 3- to 5-month-old 3xTg-AD mice than in nonTg mice of the same age.”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Resende et al. (2008)
Among these markers were decreased levels of GSH, increased levels of GSSG, and increased levels of malondialdehyde (MDA).
“Among these markers were decreased levels of GSH, increased levels of GSSG, and increased levels of malondialdehyde (MDA), a marker for lipid peroxidation.”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Resende et al. (2008)
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- Authors
- Resende, R., Moreira, P. I., Proença, T., Deshpande, A., Busciglio, J., Pereira, C., & Oliveira, C. R.
- Affiliations
- Centro de Neurociências e Biologia Celular (PT)
- Unidade Local de Saúde de Coimbra (PT)
- University of California, Irvine (US)
- Corresponding author
- Pereira, Cláudia
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 44
- Issue
- 12
- Pages
- 2051-2057
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2068318042
- Cited by
- 343
- References
- 9
- Citations by year
- 2026: 13 · 2025: 8 · 2024: 15 · 2023: 18 · 2022: 18 · 2021: 16 · 2020: 27 · 2019: 17 · 2018: 20 · 2017: 13 · 2016: 22 · 2015: 21 · 2014: 27 · 2013: 16 · 2012: 24
- FWCI
- 14.27
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Funders
- Fundação para a Ciência e a Tecnologia (SFRH/BD/11005/2002)
- 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, oxidative stress, amyloid-beta, amyloid-beta oligomerization, lipid peroxidation, reduced glutathione, vitamin E, glutathione peroxidase, superoxide dismutase, antioxidants, neurofibrillary tangles, amyloid plaques
- MeSH terms
- Alzheimer Disease, Animals, Antioxidants, Brain, Glutathione, Mice, Transgenic, Vitamin E, Lipid Peroxidation, Oxidative Stress, Mice, Plaque, Amyloid
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