Single-Molecule Imaging of Individual Amyloid Protein Aggregates in Human Biofluids
详细信息 查看全文
- 作者：Mathew H. Horrocks ; Steven F. Lee ; Sonia Gandhi ; Nadia K. Magdalinou ; Serene W. Chen ; Michael J. Devine ; Laura Tosatto ; Magnus Kjaergaard ; Joseph S. Beckwith ; Henrik Zetterberg ; Marija Iljina ; Nunilo Cremades ; Christopher M. Dobson ; Nicholas W. Wood ; David Klenerman
- 刊名：ACS Chemical Neuroscience
- 出版年：2016
- 出版时间：March 16, 2016
- 年：2016
- 卷：7
- 期：3
- 页码：399-406
- 全文大小：471K
- ISSN：1948-7193
文摘
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.