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

Hideki Hayashi, Urule Igbavboa, Hiroki Hamanaka, Mariko Kobayashi, Shinobu C. Fujita, Gibson W. Wood, Katsuhiko Yanagisawa

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

inheritance of the apolipoprotein (apoE) ε4 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 ∼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.

Original languageEnglish (US)
Pages (from-to)383-386
Number of pages4
JournalNeuroreport
Volume13
Issue number4
DOIs
StatePublished - Mar 25 2002

Keywords

  • Alzheimer's disease
  • Apolipoprotein E
  • Cholesterol
  • Knock-in mouse
  • Synaptic plasma membrane

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