APP and PS-1 mutations induce brain oxidative stress independent of dietary cholesterol: implications for Alzheimer’s disease

doi:10.1016/j.neulet.2004.06.077

Neuroscience Letters

Volume 368, Issue 2, 23 September 2004, Pages 148-150

https://doi.org/10.1016/j.neulet.2004.06.077 Get rights and content

Abstract

Epidemiological and biochemical studies strongly implicate a role for cholesterol in the pathogenesis of Alzheimer’s disease (AD). Mutation in the PS-1 and APP genes, which increases production of the highly amyloidogenic amyloid β-peptide (Aβ42), is the major cause of familial AD. The AD brain is under significant oxidative stress, including protein oxidation and lipid peroxidation. In the present study, protein oxidation and lipid peroxidation were compared in the brain homogenates from knock-in mice expressing mutant human PS-1 and APP in relation to the intake of dietary cholesterol. The APP and PS-1 mice displayed increased oxidative stress as measured by protein oxidation and lipid peroxidation, independent of dietary cholesterol. These results are discussed with reference to proposed therapeutic strategies of AD.

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Acknowledgments

This research was supported in part by NIH to D.A.B. [AG-10836; AG-05119] and G.L.W. [AG10546; Alzheimer’s Assoc., IIRG-01-2654]

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Transgenic mice which express either PS1 or PS2 constitute another group of AD transgenes that exhibit increased levels of amyloid (Herreman et al., 1999; Huang et al., 2003; Hwang et al., 2002; Janus et al., 2000a; Shen et al., 1997). Age-related NTF-like inclusions, excessive age-related neuronal and synaptic loss as well as vascular pathology and increased protein oxidation have been reported in PS mutant mice (Elder et al., 2010b; Lazarov et al., 2006; Mohmmad Abdul et al., 2004; Tanemura et al., 2006). Although, elevations of Aβ42 are noticeable in PS transgenes, Aβ40 is not significantly affected.
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APP and PS-1 mutations induce brain oxidative stress independent of dietary cholesterol: implications for Alzheimer’s disease

Abstract

Section snippets

Acknowledgments

Anal. Biochem.

Adv. Cell Aging Gerontol.

Lancet

Brain Res.

Neurobiol. Dis.

Exp. Neurol.

Lipid binding to amyloid beta-peptide aggregates: preferential binding of cholesterol as compared with phosphatidylcholine and fatty acids

J. Neurochem.

Brain cholesterol: long secret life behind a barrier

Arterioscler. Thromb. Vasc. Biol.

Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress

Free Radic. Biol. Med.

Increased amyloid-β42 in brains of mice expressing mutant presenilin 1

Nature