β-Amyloid 25 to 35 Is Intercalated in Anionic and Zwitterionic Lipid Membranes to Different Extents

Abstract

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.

Lipid‐induced conformational transition of the amyloid core fragment Aβ(28–35) and its A30G and A30I mutants

“…Our results are in agreement with the study of Terzi et al (1997) and are in partial agreement with Dante et al [49]. In that case, Ab (28)(29)(30)(31)(32)(33)(34)(35) bound electrostatically to the negatively charged membrane only under physiological conditions.…”

Structure of the Amyloid-β (1−42) Monomer Absorbed To Model Phospholipid Bilayers: A Molecular Dynamics Study

“…While oligomerization does occur naturally in solution, there are other possible factors that may catalyze this reaction. Recent work [5][6][7][8][9][10][11][12][13][14][15][16] has demonstrated that cell membranes may play a significant catalytic role in increasing A aggregation rates. The A peptide is derived from the transmembrane amyloid precursor protein (APP).…”

Membrane Fusogenic Activity of the Alzheimer's Peptide Aβ(1–42) Demonstrated by Small-Angle Neutron Scattering

“…9 In our previous investigations, we had applied neutron diffraction and selective deuteration to localize the short peptide Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), a toxic fragment of Aβ, into lipid bilayers of different surface charge and composition. [10][11][12] In the present study, the interaction of the most abundant Aβ in senile plaques, that is, Aβ , with unilamellar lipid vesicles (ULVs) is investigated by small-angle neutron scattering (SANS). SANS is a well-established technique for the investigation of lipid vesicles 13 and the change of the parameters describing their structure in different conditions.…”