Brain membrane cholesterol domains, aging and amyloid beta-peptides

W. Gibson Wood, Friedhelm Schroeder, Urule Igbavboa, Nicolai A. Avdulov, Svetlana V. Chochina

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. These domains consist of the exofacial and cytofacial leaflets, cholesterol pools, annular lipids, and lipid rafts. Membrane lipid domains have been proposed to be involved in a variety of different functions including e.g. signal transduction, lipid transport and metabolism, and cell growth. Membrane lipid domains have been identified in brain and can be modified by different experimental conditions, aging and certain neurodegenerative diseases. Recent data reveal the very interesting possibility that membrane lipid domains may be a target of Alzheimer's disease. There is a growing body of evidence showing an association between cholesterol and Alzheimer's disease, and cholesterol is a major component of membrane lipid domains. Here we discuss recent data on brain membrane lipid domains emphasizing the structural and functional role of cholesterol. In addition, lipid domains and aging, and the potential interaction of lipid domains and amyloid beta-peptides (Aβ) that are a major component of senile plaques in brains of Alzheimer's patients are considered. We propose that age changes in the asymmetric distribution of cholesterol in contrast to total or bulk cholesterol in neuronal plasma membranes provides a cooperative environment for accumulation of Aβ in plasma membranes and the accumulation of Aβ is due in part to a direct physico-chemical interaction with cholesterol in the membrane exofacial or outer leaflet.

Original languageEnglish (US)
Pages (from-to)685-694
Number of pages10
JournalNeurobiology of Aging
Volume23
Issue number5
DOIs
StatePublished - Sep 2002

Bibliographical note

Funding Information:
Supported in part by grants from the National Institutes of Health (AG-11056, AA-10806, 1POAG-18357) and the Medical Research Program of the Department of Veterans Affairs.

Keywords

  • Aging
  • Alzheimer's disease
  • Amyloid beta-peptides
  • Annular lipids
  • Caveolae
  • Caveolin
  • Cholesterol
  • Fatty acid binding proteins
  • Lipid domains
  • Lipid rafts
  • Neurons
  • Sterol carrier protein-2

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