Brain β-amyloid accumulation in transgenic mice expressing mutant superoxide dismutase 1

Abstract

Oxidative stress is implicated in both the deposition and pathogenesis of β-amyloid (Aβ) protein in Alzheimer's disease (AD). Accordingly, overexpression of the antioxidant enzyme superoxide dismutase 1 (SOD1) in neuronal cells and transgenic AD mice reduces Aβ toxicity and accumulation. In contrast, mutations in SOD1 associated with amyotrophic lateral sclerosis (ALS) confer enhanced pro-oxidative enzyme activities. We therefore examined whether ALS-linked mutant SOD1 overexpression in motor neuronal cells or transgenic ALS mice modulates Aβ toxicity or its accumulation in the brain. Aggregated, but not freshly solubilised, substrate-bound Aβ peptides induced degenerative morphology and cyt..