Real-time observation of model membrane dynamics induced by Alzheimerʹs amyloid beta

Amyloid beta (Aβ) has been strongly implicated in inducing neurotoxicity in the pathology of Alzheimerʹs 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 Aβ-40 molecular assemblies (species). We used cell-sized lipid vesicles to enable the direct observation of these changes. We found three 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. Oligomeric Aβ exhibited the highest tendency to cause membrane fluctuation and transformations. Interestingly, mature fibrils, which are often considered inert species, also induced profound membrane changes. Furthermore, we imaged the localization of pre-fibrillar species on membranes. The real-time observation of these morphological transformations, which can be missed in a discretised analysis, may help to unlock the mechanisms of ADʹs Aβ-induced neuro-degeneration.