Direct observations of amyloid β self-assembly in live cells provide insights into differences in the kinetics of Aβ(1-40) and Aβ(1-42) aggregation

Chem Biol. 2014 Jun 19;21(6):732-42. doi: 10.1016/j.chembiol.2014.03.014. Epub 2014 May 22.


Insight into how amyloid β (Aβ) aggregation occurs in vivo is vital for understanding the molecular pathways that underlie Alzheimer's disease and requires new techniques that provide detailed kinetic and mechanistic information. Using noninvasive fluorescence lifetime recordings, we imaged the formation of Aβ(1-40) and Aβ(1-42) aggregates in live cells. For both peptides, the cellular uptake via endocytosis is rapid and spontaneous. They are then retained in lysosomes, where their accumulation leads to aggregation. The kinetics of Aβ(1-42) aggregation are considerably faster than those of Aβ(1-40) and, unlike those of the latter peptide, show no detectable lag phase. We used superresolution fluorescence imaging to examine the resulting aggregates and could observe compact amyloid structures, likely because of spatial confinement within cellular compartments. Taken together, these findings provide clues as to how Aβ aggregation may occur within neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / biosynthesis
  • Amyloid beta-Peptides / metabolism*
  • Cell Survival
  • Humans
  • Kinetics
  • Peptide Fragments / biosynthesis
  • Peptide Fragments / metabolism*
  • Protein Aggregates*
  • Protein Aggregation, Pathological*
  • Tumor Cells, Cultured


  • Amyloid beta-Peptides
  • Peptide Fragments
  • Protein Aggregates
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)