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International Journal of Alzheimer’s Disease
Volume 2010, Article ID 752804, 12 pages
http://dx.doi.org/10.4061/2010/752804
Research Article

Choline Modulation of the Aβ P1-40 Channel Reconstituted into a Model Lipid Membrane

Dipartimento Farmaco-Biologico, Università degli Studi di Bari, Via E. Orabona 4, 70126 Bari, Italy

Received 26 July 2010; Accepted 10 November 2010

Academic Editor: Hyoung-gon Lee

Copyright © 2010 Daniela Meleleo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Nicotinic acetylcholine receptors (AChRs), implicated in memory and learning, in subjects affected by Alzheimer's disease result altered. Stimulation of α7-nAChRs inhibits amyloid plaques and increases ACh release. β-amyloid peptide (AβP) forms ion channels in the cell and model phospholipid membranes that are retained responsible in Alzheimer disease. We tested if choline, precursor of ACh, could affect the AβP1-40 channels in oxidized cholesterol (OxCh) and in palmitoyl-oleoyl-phosphatidylcholine (POPC):Ch lipid bilayers. Choline concentrations of 5 × 10−11 M–1.5 × 10−8 M added to the cis- or trans-side of membrane quickly increased AβP1-40 ion channel frequency (events/min) and ion conductance in OxCh membranes, but not in POPC:Ch membranes. Circular Dichroism (CD) spectroscopy shows that after 24 and 48 hours of incubation with AβP1-40, choline stabilizes the random coil conformation of the peptide, making it less prone to fibrillate. These actions seem to be specific in that ACh is ineffective either in solution or on AβP1-40 channel incorporated into PLMs.