title: Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse.
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.
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Nishida
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
authors.forename: Tsubura
authors.initials: T
authors.lastname: Takahashi
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchihara
authors.forename: Kou-ichi
authors.initials: K
authors.lastname: Jishage
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D014811:Vitamin E Deficiency / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D016229:Amyloid beta-Peptides