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Single-molecule characterization of salivary protein aggregates from Parkinson's disease patients: a pilot study.

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Furlepa, Martin 
Zhang, Yu P 
Kahanawita, Lakmini 
Vivacqua, Giorgio 


Saliva is a convenient and accessible biofluid that has potential as a future diagnostic tool for Parkinson's disease. Candidate diagnostic tests for Parkinson's disease to date have predominantly focused on measurements of α-synuclein in CSF, but there is a need for accurate tests utilizing more easily accessible sample types. Prior studies utilizing saliva have used bulk measurements of salivary α-synuclein to provide diagnostic insight. Aggregate structure may influence the contribution of α-synuclein to disease pathology. Single-molecule approaches can characterize the structure of individual aggregates present in the biofluid and may, therefore, provide greater insight than bulk measurements. We have employed an antibody-based single-molecule pulldown assay to quantify salivary α-synuclein and amyloid-β peptide aggregate numbers and subsequently super-resolved captured aggregates using direct Stochastic Optical Reconstruction Microscopy to describe their morphological features. We show that the salivary α-synuclein aggregate/amyloid-β aggregate ratio is increased almost 2-fold in patients with Parkinson's disease (n = 20) compared with controls (n = 20, P < 0.05). Morphological information also provides insight, with saliva from patients with Parkinson's disease containing a greater proportion of larger and more fibrillar amyloid-β aggregates than control saliva (P < 0.05). Furthermore, the combination of count and morphology data provides greater diagnostic value than either measure alone, distinguishing between patients with Parkinson's disease (n = 17) and controls (n = 18) with a high degree of accuracy (area under the curve = 0.87, P < 0.001) and a larger dynamic range. We, therefore, demonstrate for the first time the application of highly sensitive single-molecule imaging techniques to saliva. In addition, we show that aggregates present within saliva retain relevant structural information, further expanding the potential utility of saliva-based diagnostic methods.



Parkinson’s disease, amyloid-β, saliva, single-molecule imaging, α-synuclein

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Brain Commun

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Oxford University Press
Royal Society (RSRP\R\210003)
Medical Research Council (MR/R007446/1)
The work was supported by a grant from Parkinson’s UK (G-1901), by the UK Dementia Research Institute which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council (MR/R007446/1), Alzheimer’s Society and Alzheimer’s Research UK, and by the Royal Society. CHWG is supported by the Medical Research Council (MR/W029235/1), and the NIHR Cambridge Biomedical Research Centre (NIHR203312). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.