Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease
Open accessAbstract
Alzheimer's disease (AD) is a neurodegenerative disease characterized by impaired cognitive function and the deposition of extracellular amyloid plaques and intracellular tangles. Although the proximal cause of AD is not well understood, it is clear that amyloid-β (Aβ) plays a critical role in AD pathology. Recent studies also implicate mitochondrial abnormalities in AD. We investigated this idea by crossing mice that overexpress mitochondrial superoxide dismutase (SOD-2) with the Tg2576 mouse model of AD that overexpresses the human amyloid precursor protein carrying the Swedish mutation (K670N:M671L). We found that overexpression of SOD-2 decreased hippocampal superoxide, prevented AD-related learning and memory deficits, and reduced Aβ plaques. Interestingly, SOD-2 overexpression did not affect the absolute levels of Aβ 1–40 and Aβ 1–42 , but did significantly reduce the Aβ 1–42 to Aβ 1–40 ratio, thereby shifting the balance toward a less amyloidogenic Aβ composition. These findings directly link mitochondrial superoxide to AD pathology and demonstrate the beneficial effects of a mitochondrial anti-oxidant enzyme, hence offering significant therapeutic implications for AD.
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Reduction of MnSOD levels accelerates AD-like pathology in a transgenic mouse model of AD.
“reduction of mitochondrial superoxide dismutase (MnSOD) levels accelerates AD-like pathology in a transgenic mouse model of AD”
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 Massaad et al., 2009
Evidence supports a causative role for nitro-oxidative modifications in mediating early synaptic degeneration and cognitive decline in AD.
“Evidence supports a causative role for these modifications in mediating the early synaptic degeneration and cognitive decline in AD”
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 Massaad et al., 2009
Overexpression of MnSOD decreases Aβ-processing in a transgenic mouse AD model.
“overexpression of MnSOD decreases Aβ-processing”
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 Massaad et al., 2009
Overexpression of MnSOD preserves synaptic integrity in a transgenic mouse AD model.
“preserves synaptic integrity”
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 Massaad et al., 2009
Overexpression of MnSOD eliminates the earliest cognitive deficits in a transgenic mouse AD model.
“eliminates the earliest cognitive deficits in a transgenic mouse AD model”
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 Massaad et al., 2009
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Revisiting an age-old question regarding oxidative stress
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- Authors
- Massaad, C. A., Washington, T. M., Pautler, R. G., & Klann, E.
- Affiliations
- Baylor College of Medicine (US)
- New York University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-08-11
- Volume
- 106
- Issue
- 32
- Pages
- 13576-13581
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2726352
- OpenAlex
- W2050860441
- Cited by
- 223
- References
- 5
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 11 · 2023: 13 · 2022: 16 · 2021: 19 · 2020: 15 · 2019: 7 · 2018: 11 · 2017: 14 · 2016: 16 · 2015: 5 · 2014: 17 · 2013: 12 · 2012: 15
- FWCI
- 9.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- American Health Assistance Foundation
- National Institutes of Health (N S04738 4, N S03400 7)
- National Institute on Aging (AG029977, R01AG029977)
- National Heart, Lung, and Blood Institute (T32HL007676)
- National Institute of Neurological Disorders and Stroke (R37NS034007, NS-047384, R01NS034007, R29NS034007, NS-034007, R01NS047384)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- Alzheimer's disease, manganese superoxide dismutase, mitochondrial superoxide dismutase, amyloid-beta, amyloid plaques, learning and memory impairment, Tg2576 mice, amyloid precursor protein, mitochondrial dysfunction, oxidative stress, antioxidant therapy
- MeSH terms
- Superoxide Dismutase 2, Aging, Alzheimer Disease, Animals, Disease Models, Animal, Hippocampus, Memory Disorders, Mice, Transgenic, Superoxides, Superoxide Dismutase, Amyloid beta-Peptides, Mice, Plaque, Amyloid
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