Beta-amyloid 25 to 35 is intercalated in anionic and zwitterionic lipid membranes to different extents.
Neuronal plasma membranes are thought to be the primary target of the neurotoxic beta-amyloid peptides (Abeta) in the pathogenesis of the Alzheimer's disease. Histologically, Abeta peptides are observed as extracellular macroscopic senile plaques, and most biophysical techniques have indicated the presence of Abeta close to the lipid headgroup region but not in the core of the membrane bilayers. The focus of this study is an investigation of the interaction between Abeta and lipid bilayers from a structural point of view. Neutron diffraction with the use of selectively deuterated amino acids has allowed us to determine unambiguously the position of the neurotoxic fragment Abeta (25-35) in the membrane. Two populations of the peptide are detected, one in the aqueous vicinity of the membrane surface and the second inside the hydrophobic core of the lipid membrane. The location of the C terminus was studied in two different lipid compositions and was found to be dependent on the surface charge of the membrane. The localization of beta-amyloid peptides in cell membranes will offer new insights on their mechanism in the neurodegenerative process associated with Alzheimer's disease and might provide clues for therapeutic developments.
Dante
Silvia
S
Physical Biochemistry, Darmstadt University of Technology, Petersenstrasse 22, D-64287 Darmstadt, Germany. silvia.dante@hmi.de
Hauss
Thomas
T
Dencher
Norbert A
NA
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000838:Anions; D055592:Biophysical Phenomena; D001703:Biophysics; D017666:Deuterium Oxide / Q000737:chemistry; D006801:Humans; D007477:Ions; D008051:Lipid Bilayers / Q000737:chemistry*; D015233:Models, Statistical; D009502:Neutrons; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry
D016229:Amyloid beta-Peptides; D000838:Anions; D007477:Ions; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010455:Peptides; D010713:Phosphatidylcholines; C074636:amyloid beta-protein (25-35); D017666:Deuterium Oxide; C028694:1-palmitoyl-2-oleoylphosphatidylcholine