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Amyloid‐β Deposition in Alzheimer Transgenic Mice Is Associated with Oxidative Stress
Author(s) -
Smith Mark A.,
Hirai Keisuke,
Hsiao Karen,
Pappolla Miguel A.,
Harris Peggy L. R.,
Siedlak Sandra L.,
Tabaton Massimo,
Perry George
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70052212.x
Subject(s) - oxidative stress , genetically modified mouse , amyloid (mycology) , pathogenesis , alzheimer's disease , transgene , amyloid precursor protein , in vivo , oxidative phosphorylation , biology , pathology , disease , medicine , endocrinology , biochemistry , genetics , gene
Increased awareness for a role of oxidative stress in the pathogenesis of Alzheimer's disease has highlighted the issue of whether oxidative damage is a fundamental step in the pathogenesis or instead results from disease‐associated pathology. In vitro experiments support both possibilities: Oxidative stress increases amyloid‐β production, and, conversely, amyloid‐β increases oxidative damage. To address the relationship between amyloid‐β and oxidative stress in vivo, we examined, using an array of oxidative markers, transgenic mice that overexpress amyloid‐β precursor protein and, as in Alzheimer's disease, develop characteristic amyloid‐β deposits within the brain parenchyma. Transgenic animals show the same type of oxidative damage that is found in Alzheimer's disease, and it is important that this damage directly correlates with the presence of amyloid‐β deposits. The significance of these studies is twofold. First, they provide evidence that amyloid‐β and oxidative damage are inextricably linked in vivo. Second, they support the use of transgenic animals for the development of antioxidant therapeutic strategies.