Amyloid beta-protein interactions with membranes and cholesterol: Causes or casualties of Alzheimer's disease

W. Gibson Wood, Gunter P. Eckert, Urule Igbavboa, Walter E. Müller

Research output: Contribution to journalReview articlepeer-review

135 Scopus citations

Abstract

Amyloid beta-protein (Aβ) is thought to be one of the primary factors causing neurodegeneration in Alzheimer's disease (AD). This protein is an amphipathic molecule that perturbs membranes, binds lipids and alters cell function. Several studies have reported that Aβ alters membrane fluidity but the direction of this effect has not been consistently observed and explanations for this lack of consistency are proposed. Cholesterol is a key component of membranes and cholesterol interacts with Aβ in a reciprocal manner. Aβ impacts on cholesterol homeostasis and modification of cholesterol levels alters Aβ expression. In addition, certain cholesterol lowering drugs (statins) appear to reduce the risk of AD in human subjects. However, the role of changes in the total amount of brain cholesterol in AD and the mechanisms of action of statins in lowering the risk of AD are unclear. Here we discuss data on membranes, cholesterol, Aβ and AD, and propose that modification of the transbilayer distribution of cholesterol in contrast to a change in the total amount of cholesterol provides a cooperative environment for Aβ synthesis and accumulation in membranes leading to cell dysfunction including disruption in cholesterol homeostasis.

Original languageEnglish (US)
Pages (from-to)281-290
Number of pages10
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1610
Issue number2
DOIs
StatePublished - Mar 10 2003

Bibliographical note

Funding Information:
This study was supported by NIH grant (1P0AG-18357), NATO Collaborative Linkage Grant (976648) and the Medical Research Program of the Department of Veterans Affairs.

Keywords

  • Alzheimer's disease
  • Amyloid beta-protein
  • Apolipoprotein E
  • Cholesterol
  • Fluidity
  • Lipid raft
  • Statin

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