Electrophysiologic properties of channels induced by Aβ25–35 in planar lipid bilayers

Abstract

Aβ25–35, a fragment of the neurotoxic amyloid beta protein Aβ1–42 found in the brain of Alzheimer patients, possesses amyloidogenic, neurotoxins and channel forming abilities similar to that of Aβ1–42. We have previously reported that Aβ25–35 formed voltage-dependent, relatively nonselective, ion-permeable channels in planar lipid bilayers [38,39,51,53]. Here, we show that Aβ25–35 formed channels in both solvent-containing and solvent-free bilayers. We also report that for Aβ25–35, channel forming activity was dependent on ionic strength, membrane lipid composition, and peptide concentration, but not on pH. Lower ionic strength and negatively charged lipids increased channel formation activity, while cholesterol decreased activity. The nonlinear function relating [Aβ25–35] and membrane activity suggests that aggregation of at least three monomers is required for channel formation.