Observation with high-speed AFM of the effect of beta amyloid on neuronal membranes with relevance to mechanisms of Alzheimer’s Disease

The high-speed AFM developed in Bristol is unique in its ability to image lipid cell membranes. We will apply HS AFM to observe the effects of amyloid oligomers on cell membranes at the nanoscale. The real-time movies will be analyzed to charactise the nature of disruption resulting from amyloid in the environment. These high-speed AFM experiments will be initially on healthy membranes and then on (Alzheimer) diseased membranes. The hormone, melatonin, has been suggested to have preventative effects in the development of Alzhiemer’s Disease. We will introduce melatonin into the membrane and repeat the HS AFM study while adding amyloid.

Alzheimer's Disease is characterised by the build up of plaques and fibres of beta amyloid, which is part of a protein naturally in the brain. These pieces of this protein are very 'sticky' and can stick to each other for from the fibres and plaques. However, it is thought that smaller aggregates of these molecules, oligomers, are toxic agents to brain cells and not the plaques. We have invented a special type of microscope which can follow the effect of the oligomers as they interact with the surface of the brain cells. We will also look at the effect of the supplement, melatonin, which is credited with acting as a possible preventative of Alzheimer's Disease.