Cholesterol is increased in the exofacial leaflet of synaptic plasma membranes of human apolipoprotein E4 knock-in mice.
Inheritance of the apolipoprotein (apoE) epsilon4 allele is a risk factor for developing Alzheimer's 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 approximately 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.
Hayashi
Hideki
H
Department of Dementia Research, National Institute for Longevity Sciences, 36-3 Gengo, Morioka, Obu 474-8522, Japan.
Igbavboa
Urule
U
Hamanaka
Hiroki
H
Kobayashi
Mariko
M
Fujita
Shinobu C
SC
Wood
W Gibson
WG
Yanagisawa
Katsuhiko
K
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000818:Animals; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008051:Lipid Bilayers; D002784:Cholesterol