Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease

• Author(s): Resende, Rosa ; Moreira, Paula Isabel ; Proença, Teresa ; Deshpande, Atul ; Busciglio, Jorge ; Pereira, Cláudia ; Oliveira, Catarina Resende
• Date: 2008
• Persistent ID: http://hdl.handle.net/10316/4674
• Origin: Estudo Geral - Universidade de Coimbra
• Subject(s): Alzheimer's disease; 3×Tg-AD mouse; Oxidative stress; Lipid peroxidation; Antioxidants; Free radicals
• Document Type: Article
• Language: English

Description

Alzheimer disease (AD) is a neurodegenerative disease which is characterized by the presence of extracellular senile plaques mainly composed of amyloid-[beta] peptide (A[beta]), intracellular neurofibrillary tangles, and selective synaptic and neuronal loss. AD brains revealed elevated levels of oxidative stress markers which have been implicated in A[beta]-induced toxicity. In the present work we addressed the hypothesis that oxidative stress occurs early in the development of AD and evaluated the extension of the oxidative stress and the levels of antioxidants in an in vivo model of AD, the triple-transgenic mouse, which develops plaques, tangles, and cognitive impairments and thus mimics AD progression in humans. We have shown that in this model, levels of antioxidants, namely, reduced glutathione and vitamin E, are decreased and the extent of lipid peroxidation is increased. We have also observed increased activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. These alterations are evident during the A[beta] oligomerization period, before the appearance of A[beta] plaques and neurofibrillary tangles, supporting the view that oxidative stress occurs early in the development of the disease. http://www.sciencedirect.com/science/article/B6T38-4S575T6-1/1/a8327ebd74cb7baf97f9aa0ac56dbd9b