Membrane-mediated mechanism of amyloid oligomer toxicity in Alzheimer's Disease.

There is strong evidence, that soluble amyloid $\beta $ (A$\beta )$ oligomers, involved in Alzheimer's Disease, are the primary toxic species of A$\beta $, although the mechanism of cell toxicity is very much debated [1]. Neutron reflectivity and electrical impedance spectroscopy assess the structural impact of A$\beta $ (1-42) oligomers and their effect on the electrical properties of a tethered phosphocholine model membrane. Two distinct and reversible peptide -- membrane interactions were revealed: At low A$\beta $ concentrations an equal incorporation of A$\beta $ into both lipid leaflets and a compaction of the lipid membrane takes place. A$\beta $ locally lowers the dielectric barrier for ion transport and the activation energy for ion transport through the bilayer remains significantly above that of a water-filled transmembrane pore. At high A$\beta $ concentrations, an additional membrane thinning is observed. [1] D. Eliezer, J. Gen. Physiol. 128:631 (2006).