Apolipoprotein E mediates sulfatide depletion in animal models of Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:31

Article

Cheng, Hua¹  Zhou, Yunhua⁵  Holtzman, David M.^2,3,4  Han, Xianlin¹ 

[1] Washington Univ, Sch Med, Dept Internal Med, Div Bioorgan Chem & Mol Pharmacol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA

[5] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China

关键词: Alzheimer's disease;    Apolipoprotein E;    APP transgenic mice;    PDAPP;    Shotgun lipidomics;    Sphingolipidomics;    Sulfatide;    Tg2576;   

DOI  :  10.1016/j.neurobiolaging.2008.07.020

来源: Elsevier

【 摘 要 】

Herein, we tested a recently proposed working model of apolipoprotein E (apoE)-mediated sulfatide metabolism/trafficking/homeostasis with two well-characterized amyloid precursor protein (APP) transgenic (Tg) animal models of Alzheimer's disease (AD) (i.e., APP(V717F) and APPsw) on a wild-type murine apoE background or after being bred onto an Apoe-1-background. As anticipated, lipidomics analysis demonstrated that the sulfatide levels in brain tissues were reduced beginning at approximately 6 months of age in APPv717F Tg, Apoe(+/+) mice and at 9 months of age in APPsw Tg, Apoe(+/+) mice relative to their respective non-APP Tg littermates. This reduction increased in both APP Tg mice as they aged. In contrast, sulfatide depletion did not occur in APP Tg, Apoe(-/-) animals relative to the Apoe(-/-)littermates. The lack of sulfatide depletion in APP Tg, Apoe(-/-) mice strongly supports the role of apoE in the deficient sulfatide content in APP Tg, Apoe(+/+) mice. Collectively, through different animal models of AD, this study provides evidence for an identified biochemical mechanism that may be responsible for the sulfatide depletion at the earliest stages of AD. (C) 2008 Elsevier Inc. All rights reserved.

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