Membrane disruption by Alzheimer beta-amyloid peptides mediated through specific finding to either phospholipids or gangliosides - Implications for neurotoxicity

Increasing evidence implicates A beta peptides as neurotoxic agents in Alzheimer's disease. We investigated one possible mechanism of neurotoxicity, namely A beta-membrane lipid interactions, We find that A beta disruption membranes containing acidic phospholipids. This disruption is greater at slightly acidic pH (characteristic of endosomes) than at neutral pH (characteristic of the extracellular space). This pH dependence suggests that A beta has the capacity to disrupt endosomal and plasma membranes, and this disruption could account, at least in part, for the observed neurotoxic effects of the peptide. We also find that gangliosides induce A beta to adopt a novel alpha/beta conformation at neutral pH.