Distribution and fluidizing action of soluble and aggregated amyloid β-peptide in rat synaptic plasma membranes

The effects of soluble and aggregated amyloid P-peptide (AP) on cortical synaptic plasma membrane (SPM) structure were examined using small angle x-ray diffraction and fluorescence spectroscopy approaches, Electron density profiles generated from the x-ray diffraction data demonstrated that soluble and aggregated A beta(1-40) peptides associated with distinct regions of the SPM, The width of the SPM samples, including surface hydration, was 84 Angstrom at 10 degrees C, Following addition of soluble A beta(1-40), there was a broad increase in electron density in the SPM hydrocarbon core +/-0-15 Angstrom from the membrane center, and a reduction in hydrocarbon core width by 6 Angstrom. By contrast, aggregated A beta(1-40) contributed electron density to the phospholipid headgroup/hydrated surface of the SPM +/-24-37 Angstrom from the membrane center, concomitant with an increase in molecular volume in the hydrocarbon core, The SPM interactions observed for A beta(1-40) were reproduced in a brain lipid membrane system, In contrast to A beta(1-40), aggregated A beta(1-42) intercalated into the lipid bilayer hydrocarbon core +/-0-12 Angstrom from the membrane center. Fluorescence experiments showed that both soluble and aggregated A beta(1-40) significantly increased SPM bulk and protein annular fluidity, Physico chemical interactions of AP with the neuronal membrane may contribute to mechanisms of neurotoxicity, independent of specific receptor binding.