Cholesterol is increased in the exofacial leaflet of synaptic plasma membranes of human apolipoprotein E4 knock-in mice

被引:69
作者
Hayashi, H
Igbavboa, U
Hamanaka, H
Kobayashi, M
Fujita, SC
Wood, WG
Yanagisawa, K
机构
[1] Natl Inst Longev Sci, Dept Dementia Res, Morioka, Obu 4748522, Japan
[2] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Minneapolis, MN 55417 USA
[3] Univ Minnesota, Dept Pharmacol, Minneapolis, MN 55417 USA
[4] Mitsubishi Kagaku Inst Life Sci, Machida, Tokyo 1948511, Japan
关键词
Alzheimer's disease; apolipoprotein E; cholesterol; knock-in mouse; synaptic plasma membrane;
D O I
10.1097/00001756-200203250-00004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Inheritance of the apolipoprotein (apoE) epsilon4 allele is a risk factor for developing Alzheimers disease (AD). The purpose of the present study was to determine effects of apoE-isoforms on the transbilayer distribution of cholesterol in synaptic plasma membranes (SPM) using mice expressing human apoE3 and apoE4. Total SPM cholesterol levels did not differ among the wild-type and apoE3 and apoE4 knock-in mice. However, a striking difference was observed in the transbilayer distribution of SPM cholesterol. ApoE4 knock-in mice showed an similar to 2-fold increase in exofacial leaflet cholesterol compared with apoE3 knock-in mice and wild-type mice. The results of this study suggest that pathogenic effects of apoE4 on AD development could be closely linked to alteration of cholesterol distribution in SPM.
引用
收藏
页码:383 / 386
页数:4
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