Model-membrane morphological transformations induced by different amyloid molecular assemblies

Amyloid beta (Aß) has been strongly implicated in inducing neurotoxicity in the pathology of Alzheimer´s disease (AD). However, the underlying mechanisms remain unknown. In this study, we examined, in real-time, the spatio-temporal changes in individual model membranes induced by the presence of different Aß-40 molecular assemblies (species). We used cell-sized lipid vesicles to enable the direct observation of these changes. We found two significantly different membrane-transformation pathways. We characterized the biophysical mechanisms behind these transformations in terms of the change in inner vesicle volume and surface area. Interestingly, mature fibrils, which are often considered inert species, also induced profound membrane changes. The real-time observation of these morphological transformations, which can be missed in a discretised analysis, may help to unlock the mechanisms of Alzheimer´s Aß-induced neuro-degeneration.