MEMBRANE DISRUPTION BY ALZHEIMER BETA-AMYLOID PEPTIDES MEDIATED THROUGH SPECIFIC FINDING TO EITHER PHOSPHOLIPIDS OR GANGLIOSIDES - IMPLICATIONS FOR NEUROTOXICITY
J. Mclaurin et A. Chakrabartty, MEMBRANE DISRUPTION BY ALZHEIMER BETA-AMYLOID PEPTIDES MEDIATED THROUGH SPECIFIC FINDING TO EITHER PHOSPHOLIPIDS OR GANGLIOSIDES - IMPLICATIONS FOR NEUROTOXICITY, The Journal of biological chemistry, 271(43), 1996, pp. 26482-26489
Increasing evidence implicates A beta peptides as neurotoxic agents in
Alzheimer's disease. We investigated one possible mechanism of neurot
oxicity, namely A beta-membrane lipid interactions, We find that A bet
a disruption membranes containing acidic phospholipids. This disruptio
n is greater at slightly acidic pH (characteristic of endosomes) than
at neutral pH (characteristic of the extracellular space). This pH dep
endence 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 tha
t gangliosides induce A beta to adopt a novel alpha/beta conformation
at neutral pH.