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Updated: Aug 24, 2026
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice
Feng Li1, Noel Y Calingasan, Fangmin Yu
1Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA.
Abstract:
A growing body of evidence suggests a relationship between oxidative stress and beta-amyloid (Abeta) peptide accumulation, a hallmark in the pathogenesis of Alzheimer's disease (AD). However, a direct causal relationship between oxidative stress and Abeta pathology has not been established in vivo. Therefore, we crossed mice with a knockout of one allele of manganese superoxide dismutase (MnSOD), a critical antioxidant enzyme, with Tg19959 mice, which overexpress a doubly mutated human beta-amyloid precursor protein (APP). Partial deficiency of MnSOD, which is well established to cause elevated oxidative stress, significantly increased brain Abeta levels and Abeta plaque burden in Tg19959 mice. These results indicate that oxidative stress can promote the pathogenesis of AD and further support the feasibility of antioxidant approaches for AD therapy.
Insights
Oxidative stress exacerbates Alzheimer's disease (AD) pathology. This study shows that reduced antioxidant enzyme manganese superoxide dismutase (MnSOD) significantly increases beta-amyloid (Abeta) in the brain, supporting antioxidant therapies for AD.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Oxidative stress is linked to beta-amyloid (Abeta) accumulation in Alzheimer's disease (AD) pathogenesis.
- A direct in vivo causal link between oxidative stress and Abeta pathology remains unestablished.
Purpose of the Study:
- To investigate the in vivo causal relationship between oxidative stress and Abeta pathology in Alzheimer's disease.
- To determine if reduced antioxidant capacity promotes Abeta accumulation and plaque burden.
Main Methods:
- Crossed mice with a knockout of one allele of manganese superoxide dismutase (MnSOD) with Tg19959 mice overexpressing mutated human beta-amyloid precursor protein (APP).
- Assessed the impact of partial MnSOD deficiency (elevated oxidative stress) on brain Abeta levels and plaque burden.
Main Results:
- Partial MnSOD deficiency significantly increased brain Abeta levels in Tg19959 mice.
- Elevated oxidative stress led to a greater Abeta plaque burden in the AD mouse model.
Conclusions:
- Oxidative stress directly promotes Alzheimer's disease pathogenesis.
- Antioxidant strategies show promise for therapeutic intervention in AD.
