The modulating effect of mechanical changes in lipid bilayers caused by apoE-containing lipoproteins on Aβ induced membrane disruption

Justin Legleiter, John D. Fryer, David M. Holtzman, Tomasz Kowalewski

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A major feature of Alzheimer's disease (AD), a late-onset neurodegenerative disorder, is the ordered aggregation of the β-amyloid peptide (Aβ) into fibrils that comprise extracellular neuritic plaques found in the disease brain. One of many potential pathways for Aβ toxicity may be modulation of lipid membrane function. Here, we show by in situ atomic force microscopy (AFM) that astrocyte secreted lipoprotein particles (ASLPs) containing different isoforms of apolipoprotein E (apoE), of which the apoE4 allele is a major risk factor for the development of AD, can protect total brain lipid extract bilayers from Aβ 1-40 induced disruption. The apoE4 allele was less effective in protecting lipid bilayers from disruption compared with apoE3. Size analysis of apoE-containing ASLPs and mechanical studies of bilayer properties revealed that apoE-containing ASLPs modulate the mechanical properties of bilayers by acquiring some bilayer components (most likely cholesterol and/or oxidatively damaged lipids). Measurement of bilayer mechanical properties was accomplished with scanning probe acceleration microscopy (SPAM). These measurements demonstrated that apoE4 was also less effective in modulating mechanical properties of bilayers in comparison with apoE3. This ability of apoE to alter the mechanical properties of lipid membranes may represent a potential mechanism for the suppression of Aβ 1-40 induced bilayer disruption.

Original languageEnglish (US)
Pages (from-to)588-599
Number of pages12
JournalACS Chemical Neuroscience
Volume2
Issue number10
DOIs
StatePublished - Oct 19 2011
Externally publishedYes

Fingerprint

Lipid bilayers
Lipid Bilayers
Apolipoproteins E
Apolipoprotein E4
Lipoproteins
Apolipoprotein E3
Astrocytes
Membranes
Mechanical properties
Membrane Lipids
Brain
Scanning Probe Microscopy
Alzheimer Disease
Alleles
Lipids
Aptitude
Atomic Force Microscopy
Amyloid Plaques
Brain Diseases
Amyloid

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Physiology
  • Cognitive Neuroscience

Cite this

The modulating effect of mechanical changes in lipid bilayers caused by apoE-containing lipoproteins on Aβ induced membrane disruption. / Legleiter, Justin; Fryer, John D.; Holtzman, David M.; Kowalewski, Tomasz.

In: ACS Chemical Neuroscience, Vol. 2, No. 10, 19.10.2011, p. 588-599.

Research output: Contribution to journalArticle

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