Final Report Summary - SINGLEMOLALZHEIMER (Dissecting Alzheimer’s disease at a single molecule level) This project has been the first one to systematically apply single molecule tracking techniques to investigate the molecular basis of Alzheirmer’s disease. This approach has allowed to discover new features normally not accessible with standard methods based on data averaging. This study has contributed to add new information on the biology of the toxic Abeta petide oligomers by describing their dynamic behaviour on the plasma membrane of living cells. Additional results on the interaction of Abeta oligomers with components of the plasma membrane have also provided proof of evidence for a mechanism of toxicity that was object of debate in the past. Although the interaction of Abeta oligomers with the cellular membrane is a well-known process, the manner through which they cause cell dysfunction can depend on several factors. The findings related to this project have revealed a new potential mechanism of toxicity attributable to the loss of function of specific membrane components consequent to an alteration of their mobility caused by the binding to slowly diffusing Abeta oligomers. The dynamic behaviour and the membrane effects of toxic amyloid aggregates formed by proteins or peptides other than Abeta have also been object of investigation. Results similar to those obtained in the case of Abeta oligomers were found for amylin (involved in the development of type II diabetes) and prion sup35, supporting the hypothesis that amyloid diseases share similar mechanisms of toxicity.
