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

Nicotinic acetylcholine receptors (AChRs), implicated in memory and learning, in subjects affected by Alzheimer's disease result altered. Stimulation of α 7-nAChRs inhibits amyloid plaques and increases ACh release. β -amyloid peptide (A β P) 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 A β P1-40 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 A β P1-40 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 A β P1-40, 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 A β P1-40 channel incorporated into PLMs.