Membrane interactions and the effect of metal ions of the amyloidogenic fragment Abeta(25-35) in comparison to Abeta(1-42)

Biochim Biophys Acta. 2007 Oct;1768(10):2400-8. doi: 10.1016/j.bbamem.2007.05.004. Epub 2007 May 22.

Abstract

Abeta(1-42) peptide, found as aggregated species in Alzheimer's disease brain, is linked to the onset of Alzheimer's disease. Many reports have linked metals to inducing Abeta aggregation and amyloid plaque formation. Abeta(25-35), a fragment from the C-terminal end of Abeta(1-42), lacks the metal coordinating sites found in the full-length peptide and is neurotoxic to cortical cortex cell cultures. We report solid-state NMR studies of Abeta(25-35) in model lipid membrane systems of anionic phospholipids and cholesterol, and compare structural changes to those of Abeta(1-42). When added after vesicle formation, Abeta(25-35) was found to interact with the lipid headgroups and slightly perturb the lipid acyl-chain region; when Abeta(25-35) was included during vesicle formation, it inserted deeper into the bilayer. While Abeta(25-35) retained the same beta-sheet structure irrespective of the mode of addition, the longer Abeta(1-42) appeared to have an increase in beta-sheet structure at the C-terminus when added to phospholipid liposomes after vesicle formation. Since the Abeta(25-35) fragment is also neurotoxic, the full-length peptide may have more than one pathway for toxicity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemistry*
  • Cholesterol / chemistry
  • Lipid Bilayers / chemistry*
  • Magnetic Resonance Spectroscopy
  • Metals / chemistry*
  • Peptide Fragments / chemistry*
  • Phospholipids / chemistry

Substances

  • Amyloid beta-Peptides
  • Lipid Bilayers
  • Metals
  • Peptide Fragments
  • Phospholipids
  • amyloid beta-protein (1-42)
  • amyloid beta-protein (25-35)
  • Cholesterol