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

A beta(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 A beta aggregation and amyloid plaque formation. A beta(25-35), a fragment from the C-terminal end of A beta(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 A beta(25-35) in model lipid membrane systems of anionic phospholipids and cholesterol, and compare structural changes to those of A beta(1-42). When added after vesicle formation, A beta(25-35) was found to interact with the lipid headgroups and slightly perturb the lipid acyl-chain region; when A beta(25-35) was included during vesicle formation, it inserted deeper into the bilayer. While A beta(25-35) retained the same beta-sheet structure irrespective of the mode of addition, the longer A beta(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 A beta(25-35) fragment is also neurotoxic, the full-length peptide may have more than one pathway for toxicity. (C) 2007 Elsevier B.V. All rights reserved.