Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative stress.
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-beta production, and, conversely, amyloid-beta increases oxidative damage. To address the relationship between amyloid-beta and oxidative stress in vivo, we examined, using an array of oxidative markers, transgenic mice that overexpress amyloid-beta precursor protein and, as in Alzheimer's disease, develop characteristic amyloid-beta 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-beta deposits. The significance of these studies is twofold. First, they provide evidence that amyloid-beta and oxidative damage are inextricably linked in vivo. Second, they support the use of transgenic animals for the development of antioxidant therapeutic strategies.
Smith
M A
MA
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Hirai
K
K
Hsiao
K
K
Pappolla
M A
MA
Harris
P L
PL
Siedlak
S L
SL
Tabaton
M
M
Perry
G
G
D000447:Aldehydes / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D005625:Frontal Lobe / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics* / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D012016:Reference Values
D000447:Aldehydes; D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C027576:4-hydroxy-2-nonenal