Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease

The accumulation of the amyloid-beta peptides (A beta) is central to the development of Alzheimer's disease. The mechanism by which A beta triggers a cascade of events that leads to dementia is a topic of intense investigation. A beta self-associates into a series of complex assemblies with different structural and biophysical properties. It is the interaction of these oligomeric, protofibril and fibrillar assemblies with lipid membranes, or with membrane receptors, that results in membrane permeability and loss of cellular homeostasis, a key event in Alzheimer's disease pathology. A beta can have an array of impacts on lipid membranes, reports have included: a carpeting effect; a detergent effect; and A beta ion-channel pore formation. Recent advances imaging these interactions are providing a clearer picture of A beta induced membrane disruption. Understanding the relationship between different A beta structures and membrane permeability will inform therapeutics targeting A beta cytotoxicity.