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(Received for publication, April 3, 1996, and in revised form, June 11, 1996)
From the Department of Medical Biophysics, University of Toronto,
Toronto, Ontario M5G 2M9, Canada
Increasing evidence implicates A
Volume 271, Number 43,
Issue of October 25, 1996
pp. 26482-26489
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
-Amyloid Peptides Mediated
through Specific Binding to Either Phospholipids or Gangliosides
IMPLICATIONS FOR NEUROTOXICITY
peptides as
neurotoxic agents in Alzheimer's disease. We investigated one possible
mechanism of neurotoxicity, namely A-membrane lipid interactions. We
find that A disrupts 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 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 to adopt a novel
/ conformation at neutral pH.
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