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Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice

Li, Feng ; Calingasan, Noel Y. ; Yu, Fangmin ; Mauck, William M. ; Toidze, Marine ; Almeida, Claudia G. ; Takahashi, Reisuke H. ; Carlson, George A. ; Beal, M. Flint and Lin, Michael T. , et al. (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.

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publishing date
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}},
}