Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice
(2004) In Journal of Neurochemistry 89(5). p.1308-1312- Abstract
A growing body of evidence suggests a relationship between oxidative stress and β-amyloid (Aβ) peptide accumulation, a hall-mark in the pathogenesis of Alzheimer's disease (AD). However, a direct causal relationship between oxidative stress and Aβ 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 β-amyloid precursor protein (APP). Partial deficiency of MnSOD, which is well established to cause elevated oxidative stress, significantly increased brain Aβ levels and Aβ plaque burden in Tg19959 mice. These results indicate that oxidative stress can promote... (More)
A growing body of evidence suggests a relationship between oxidative stress and β-amyloid (Aβ) peptide accumulation, a hall-mark in the pathogenesis of Alzheimer's disease (AD). However, a direct causal relationship between oxidative stress and Aβ 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 β-amyloid precursor protein (APP). Partial deficiency of MnSOD, which is well established to cause elevated oxidative stress, significantly increased brain Aβ levels and Aβ 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.
(Less)
- author
- publishing date
- 2004-06-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- β-amyloid, Alzheimer's disease, Manganese superoxide dismutase, Oxidative stress, Transgenic mice
- in
- Journal of Neurochemistry
- volume
- 89
- issue
- 5
- pages
- 1308 - 1312
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:2642544767
- pmid:15147524
- ISSN
- 0022-3042
- DOI
- 10.1111/j.1471-4159.2004.02455.x
- language
- English
- LU publication?
- no
- id
- 0e07131b-db80-44ba-87c6-19798a66fe7f
- date added to LUP
- 2020-02-20 14:25:33
- date last changed
- 2024-06-13 12:53:14
@article{0e07131b-db80-44ba-87c6-19798a66fe7f, abstract = {{<p>A growing body of evidence suggests a relationship between oxidative stress and β-amyloid (Aβ) peptide accumulation, a hall-mark in the pathogenesis of Alzheimer's disease (AD). However, a direct causal relationship between oxidative stress and Aβ 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 β-amyloid precursor protein (APP). Partial deficiency of MnSOD, which is well established to cause elevated oxidative stress, significantly increased brain Aβ levels and Aβ 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.</p>}}, author = {{Li, Feng and Calingasan, Noel Y. and Yu, Fangmin and Mauck, William M. and Toidze, Marine and Almeida, Claudia G. and Takahashi, Reisuke H. and Carlson, George A. and Beal, M. Flint and Lin, Michael T. and Gouras, Gunnar K.}}, issn = {{0022-3042}}, keywords = {{β-amyloid; Alzheimer's disease; Manganese superoxide dismutase; Oxidative stress; Transgenic mice}}, language = {{eng}}, month = {{06}}, number = {{5}}, pages = {{1308--1312}}, publisher = {{Wiley-Blackwell}}, series = {{Journal of Neurochemistry}}, title = {{Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice}}, url = {{http://dx.doi.org/10.1111/j.1471-4159.2004.02455.x}}, doi = {{10.1111/j.1471-4159.2004.02455.x}}, volume = {{89}}, year = {{2004}}, }