Direct measurement of lipid membrane disruption connects kinetics and toxicity of Aβ42 aggregation

Research output: Contribution to journalArticle


The formation of amyloid deposits in human tissues is a defining feature of more than 50 medical disorders, including Alzheimer’s disease. Strong genetic and histological evidence links these conditions to the process of protein aggregation, yet it has remained challenging to identify a definitive connection between aggregation and pathogenicity. Using time-resolved fluorescence microscopy of individual synthetic vesicles, we show for the Aβ42 peptide implicated in Alzheimer’s disease that the disruption of lipid bilayers correlates linearly with the time course of the levels of transient oligomers generated through secondary nucleation. These findings indicate a specific role of oligomers generated through the catalytic action of fibrillar species during the protein aggregation process in driving deleterious biological function and establish a direct causative connection between amyloid formation and its pathological effects.


  • Patrick Flagmeier
  • Suman De
  • Thomas C.T. Michaels
  • Xiaoting Yang
  • Alexander J. Dear
  • Cecilia Emanuelsson
  • Michele Vendruscolo
  • Sara Linse
  • David Klenerman
  • Tuomas P.J. Knowles
  • Christopher M. Dobson
External organisations
  • University of Cambridge
  • Harvard University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
JournalNature Structural and Molecular Biology
Publication statusE-pub ahead of print - 2020 Aug 10
Publication categoryResearch