Single-molecule imaging of individual amyloid protein aggregates in human biofluids

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Mathew Harry Horrocks, University of Cambridge
  • ,
  • Steven F Lee, University of Cambridge
  • ,
  • Sonia Gandhi, University College London
  • ,
  • Nadia K Magdalinou, University College London
  • ,
  • Serene W Chen, University of Cambridge
  • ,
  • Michael J Devine, Imperial College of London
  • ,
  • Laura Tosatto, University of Cambridge
  • ,
  • Magnus Kjaergaard
  • Joseph S Beckwith, University of Cambridge
  • ,
  • Henrik Zetterberg, University of Gothenburg, University College London
  • ,
  • Marija Iljina, University of Cambridge
  • ,
  • Nunilo Cremades, University of Cambridge
  • ,
  • Christopher M Dobson, University of Cambridge
  • ,
  • Nicholas W Wood, University College London
  • ,
  • David Klenerman, University of Cambridge

The misfolding and aggregation of proteins into amyloid fibrils characterizes many neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. We report here a method, termed SAVE (single aggregate visualization by enhancement) imaging, for the ultra-sensitive detection of individual amyloid fibrils and oligomers using single-molecule fluorescence microscopy. We demonstrate that this method is able to detect the presence of amyloid aggregates of alpha-synuclein, tau and amyloid-β. In addition, we show that aggregates can also be identified in human cerebrospinal fluid (CSF). Significantly, we see a two-fold increase in the average aggregate concentration in CSF from PD patients compared to age-matched controls. Taken together, we conclude that this method provides an opportunity to characterize the structural nature of amyloid aggregates in a key biofluid, and therefore has the potential to study disease progression in both animal models and humans to enhance our understanding of neurodegenerative disorders.

OriginalsprogEngelsk
TidsskriftA C S Chemical Neuroscience
Vol/bind7
Nummer3
Sider (fra-til)399–406
ISSN1948-7193
DOI
StatusUdgivet - 22 jan. 2016
Eksternt udgivetJa

Se relationer på Aarhus Universitet Citationsformater

ID: 96608083