Monomeric and fibrillar α-synuclein exert opposite effects on the catalytic cycle that promotes the proliferation of Aβ42 aggregates

Research output: Contribution to journalArticle


The coaggregation of the amyloid-β peptide (Aβ) and α-synuclein is commonly observed in a range of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. The complex interplay between Aβ and α-synuclein has led to seemingly contradictory results on whether α-synuclein promotes or inhibits Aβ aggregation. Here, we show how these conflicts can be rationalized and resolved by demonstrating that different structural forms of α-synuclein exert different effects on Aβ aggregation. Our results demonstrate that whereas monomeric α-synuclein blocks the autocatalytic proliferation of Aβ42 (the 42-residue form of Aβ) fibrils, fibrillar α-synuclein catalyses the heterogeneous nucleation of Aβ42 aggregates. It is thus the specific balance between the concentrations of monomeric and fibrillar α-synuclein that determines the outcome of the Aβ42 aggregation reaction.


  • Sean Chia
  • Patrick Flagmeier
  • Johnny Habchi
  • Veronica Lattanzi
  • Sara Linse
  • Christopher M Dobson
  • Tuomas P J Knowles
  • Michele Vendruscolo
External organisations
  • University of Cambridge
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medicinal Chemistry


  • Alzheimer’s disease, Amyloid fibrils, Chemical kinetics, Dementia with Lewy bodies, Parkinson’s disease
Original languageEnglish
Pages (from-to)8005-8010
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number30
Publication statusPublished - 2017 Jul 25
Publication categoryResearch