Show simple item record

dc.contributor.authorHorrocks, Mathewen
dc.contributor.authorLee, Stevenen
dc.contributor.authorGandhi, Soniaen
dc.contributor.authorMagdalinou, Nadia Ken
dc.contributor.authorChen, Serene Wen
dc.contributor.authorDevine, Michael Jen
dc.contributor.authorTosatto, Lauraen
dc.contributor.authorKjaergaard, Magnusen
dc.contributor.authorBeckwith, Joseph Sen
dc.contributor.authorZetterberg, Henriken
dc.contributor.authorIljina, Marijaen
dc.contributor.authorCremades Casasin, Nuniloen
dc.contributor.authorDobson, Christopheren
dc.contributor.authorWood, Nicholas Wen
dc.contributor.authorKlenerman, Daviden
dc.date.accessioned2016-01-26T16:37:08Z
dc.date.available2016-01-26T16:37:08Z
dc.date.issued2016-01-22en
dc.identifier.citationHorrocks et al. ACS Chemical Neuroscience (2016) 7: 399-406 doi: 10.1021/acschemneuro.5b00324en
dc.identifier.issn1948-7193
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/253490
dc.description.abstractThe 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.
dc.description.sponsorshipThis research study was funded in part by the Wellcome Trust/MRC Joint Call in Neurodegeneration award (WT089698) to the UK Parkinson's Disease Consortium (UKPDC) and the NIHR rare disease translational research collaboration and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. We are also grateful to the Augustus Newman and Wolfson Foundations for their support. We thank the Royal Society for the University Research Fellowship of Dr. Steven F. Lee (UF120277).
dc.languageEnglishen
dc.language.isoenen
dc.publisherACS
dc.rightsAttribution 2.0 UK: England & Wales
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.subjectParkinson’sen
dc.subjectCSFen
dc.subjectBiomarkersen
dc.subjectSingle-moleculeen
dc.titleSingle-molecule imaging of individual amyloid protein aggregates in human biofluidsen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from ACS via http://dx.doi.org/10.1021/acschemneuro.5b00324.en
prism.endingPage406
prism.publicationDate2016en
prism.publicationNameACS Chemical Neuroscienceen
prism.startingPage399
prism.volume7en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderMRC
dc.rioxxterms.funderNIHR
dc.rioxxterms.projectidWT089698
rioxxterms.versionofrecord10.1021/acschemneuro.5b00324en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-01-22en
dc.contributor.orcidLee, Steven [0000-0003-4492-5139]
dc.contributor.orcidCremades Casasin, Nunilo [0000-0002-9138-6687]
dc.contributor.orcidKlenerman, David [0000-0001-7116-6954]
dc.identifier.eissn1948-7193
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idRoyal Society (uf120277)


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales