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Neurosci Lett. 2000 Oct 6;292(2):87-90.

Reduced antioxidant enzyme activity in brains of mice transgenic for human presenilin-1 with single or multiple mutations.

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Department of Pharmacology, Biocenter Niederursel, University of Frankfurt, Marie-Curie-Strasse 9, N 260, 60439 Frankfurt, Germany.


Alzheimer's disease-related mutations in the presenilin-1 gene (PS1) are leading to an elevated production of neurotoxic beta-amyloid 1-42 and may additionally enhance oxidative stress. Here, we provide in vivo evidence indicating that brains of transgenic mice expressing different human Alzheimer-linked PS1 mutations exhibit a reduced activity of two antioxidant enzymes. For this purpose, mice transgenic for human PS1 and for single and multiple PS1 mutations were generated. Mice with multiple PS1 mutations showed a significantly decreased activity of the antioxidant enzymes Cu/Zn superoxide dismutase and glutathione reductase already at an age of 3-4 months. As expected, this effect was less pronounced for the mice with a single PS1 mutation. By contrast, animals bearing normal human PS1 showed significantly elevated enzyme activities relative to non-transgenic littermate controls.

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