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Brain β-Amyloid Accumulation in Transgenic Mice Expressing Mutant Superoxide Dismutase 1

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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 cytotoxicity in motor neuron-like NSC-34 cells. Transfection of NSC-34 cells with human wild-type SOD1 attenuated Aβ-induced toxicity, however this neuroprotective effect was also observed for ALS-linked mutant SOD1. Analysis of the cerebral cortex, brainstem, cerebellum and olfactory bulb from transgenic SOD1G93A mice using enzyme-linked immunosorbent assay of acid–guanidine extracts revealed age-dependent elevations in Aβ levels, although not significantly different from wild-type mouse brain. In addition, brain amyloid protein precursor (APP) levels remained unaltered as a consequence of mutant SOD1 expression. We therefore conclude that mutant SOD1 overexpression promotes neither Aβ toxicity nor brain accumulation in these ALS models.

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Correspondence to Surindar S. Cheema.

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Turner, B.J., Li, QX., Laughton, K.M. et al. Brain β-Amyloid Accumulation in Transgenic Mice Expressing Mutant Superoxide Dismutase 1. Neurochem Res 29, 2281–2286 (2004). https://doi.org/10.1007/s11064-004-7037-z

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