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Single-Molecule Imaging of Individual Amyloid Protein Aggregates in Human Biofluids

Horrocks, MH; Lee, SF; Gandhi, S; Magdalinou, NK; Chen, SW; Devine, MJ; Tosatto, L; ... Klenerman, D; + view all (2016) Single-Molecule Imaging of Individual Amyloid Protein Aggregates in Human Biofluids. ACS Chemical Neuroscience , 7 (3) pp. 399-406. 10.1021/acschemneuro.5b00324. Green open access

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Abstract

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 ultrasensitive 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 α-synuclein, tau, and amyloid-β. In addition, we show that aggregates can also be identified in human cerebrospinal fluid (CSF). Significantly, we see a twofold increase in the average aggregate concentration in CSF from Parkinson’s disease 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.

Type: Article
Title: Single-Molecule Imaging of Individual Amyloid Protein Aggregates in Human Biofluids
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acschemneuro.5b00324
Publisher version: http://doi.org/10.1021/acschemneuro.5b00324
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Chemistry, Medicinal, Neurosciences, Pharmacology & Pharmacy, Neurosciences & Neurology, Parkinson's, CSF, biomarkers, single-molecule, ALPHA-SYNUCLEIN OLIGOMERS, ALZHEIMERS-DISEASE, CEREBROSPINAL-FLUID, PARKINSONS-DISEASE, THIOFLAVIN-T, PARTICLE TRACKING, BETA OLIGOMERS, FIBRIL GROWTH, FLUORESCENCE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1479180
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