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Iron Enhances the Neurotoxicity of Amyloid β

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Abstract

Brain microbleeds often occur in Alzheimer’s disease patients. Our previous studies have demonstrated that iron contributes to brain injury following intracerebral hemorrhage. This study investigated the effect of iron on amyloid β (Aβ)-mediated brain injury. There are two parts to this study. In the first part, rats received an intracaudate injection of saline, iron, Aβ 25-35, or iron + Aβ 25-35. In the second part, rats received intracaudate injection of iron + Aβ and were treated with saline or cystamine, an inhibitor of transglutaminase. Rats were killed after 24 h for brain edema measurement. DNA damage, neuronal death, and tissue-type transglutaminase (tTG) expression were also examined. We found that brain water content in the ipsilateral caudate was higher (p < 0.05) in rats injected with iron + Aβ than with iron, Aβ, or saline. Combined iron + Aβ injection also resulted in more severe DNA damage (both single- and double-strand, p < 0.01) and more Fluoro-Jade C staining (p < 0.05). Expression of tTG increased markedly in the iron + Aβ group (p < 0.05), and treatment with a tTG inhibitor reduced brain edema (p < 0.05) and reduced degenerating neurons (124 ± 25 vs. 249 ± 50/mm2 in vehicle-treated group, p < 0.05). These results suggest that increased brain iron from microbleeds may exaggerate brain Aβ toxicity and that tTG is involved in the enhanced toxicity.

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Acknowledgments

This study was supported by grants NS-017760, NS-039866, and NS-057539 from the National Institutes of Health (NIH) and 0840016N from the American Heart Association (AHA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH and AHA.

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  1. Department of Neurosurgery, University of Michigan, R5018 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA

    Lin Wang, Guohua Xi, Richard F. Keep & Ya Hua

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  1. Lin Wang
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  2. Guohua Xi
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  3. Richard F. Keep
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  4. Ya Hua
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Correspondence to Ya Hua.

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Wang, L., Xi, G., Keep, R.F. et al. Iron Enhances the Neurotoxicity of Amyloid β. Transl. Stroke Res. 3, 107–113 (2012). https://doi.org/10.1007/s12975-011-0099-8

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  • DOI: https://doi.org/10.1007/s12975-011-0099-8

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