Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse |
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Authors: | Nishida Yoichiro Yokota Takanori Takahashi Tsubura Uchihara Toshiki Jishage Kou-ichi Mizusawa Hidehiro |
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Institution: | Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan. |
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Abstract: | Increased oxidative damage is a prominent and early feature in Alzheimer disease (AD). However, whether it is a primary cause or merely a downstream consequence in AD pathology is still unknown. We previously generated alpha-tocopherol transfer protein knockout (Ttpa-/-) mice, in which lipid peroxidation in the brain was significantly increased by complete depletion of alpha-tocopherol (alpha-Toc). Here we crossed AD transgenic (APPsw) model mice (Tg2576) with Ttpa-/- mice. The resulting double-mutant (Ttpa-/- APPsw) mice showed earlier and more severe cognitive dysfunction in the Morris water maze, novel-object recognition, and contextual fear conditioning tests. They also showed increased amyloid beta-peptide (Abeta) deposits in the brain by immunohistochemical analysis, which was ameliorated with alpha-Toc supplementation. In this report we provide clear evidence indicating that chronic lipid peroxidation due to alpha-Toc depletion enhances AD phenotype in a mouse model. |
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Keywords: | Alzheimer disease Vitamin E α-Tocopherol Lipid peroxidation Oxidative stress Aβ Plaque Cognitive dysfunction Tg2576 |
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