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 f rom disease-associated pathology. In vitro experiments support both po ssibilities: Oxidative stress increases amyloid-beta production, and, conversely, amyloid-beta increases oxidative damage. To address the re lationship between amyloid-beta and oxidative stress in vivo, we exami ned, using an array of oxidative markers, transgenic mice that overexp ress amyloid-beta precursor protein and, as in Alzheimer's disease, de velop characteristic amyloid-beta deposits within the brain parenchyma . Transgenic animals show the same type of oxidative damage that is fo und in Alzheimer's disease, and it is important that this damage direc tly correlates with the presence of amyloid-beta deposits. The signifi cance of these studies is twofold. First, they provide evidence that a myloid-beta and oxidative damage are inextricably linked in vivo. Seco nd, they support the use of transgenic animals for the development of antioxidant therapeutic strategies.