Speaker
Hannah Dies
(McMaster University)
Description
The symptoms of Alzheimer’s disease do not manifest in most patients until after the age of 60, suggesting a strong link between age-related changes in the composition of brain tissue and progression of the disease. In particular, age-related changes in cholesterol and melatonin levels are currently highly discussed in the literature. We studied the interaction between two amyloid-$\beta$ peptides, amyloid-$\beta$1-42 and amyloid-$\beta$25-35, with anionic lipid model membranes containing cholesterol and melatonin. Our high resolution X-ray setup enabled us to determine the molecular structure of the membranes with sub-nanometer resolution in-situ, under physiological conditions. We determined the location and orientation of the molecules in the bilayers, and their lateral organization in the plane of the membranes. Both peptides were found to embed in the membrane core, which is believed to be crucial for the formation of oligomers. Moderate levels of cholesterol (30mol%) led to the formation of cholesterol plaques in the anionic membranes. The A$\beta$25-35 peptides were found to strongly interact with the membrane, displacing cholesterol molecules from the lipid regions into the plaques and increasing the total fraction of plaques in the membrane. The melatonin molecules were found to reside in the head group region of the membranes and increase the fluidity of the anionic membranes, in effect inhibiting the insertion of A$\beta$25-35 into the hydrocarbon core of the bilayers. We, therefore, present direct experimental evidence for an interaction between A$\beta$ peptides, melatonin and cholesterol on the level of the cell membrane and suggest an important role for age-related effects in membrane-peptide interactions.
Author
Hannah Dies
(McMaster University)
Co-authors
Dr
Maikel Rheinstadter
(McMaster University)
laura toppozini
(McMaster University)
