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

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.

Lee, Steven F (author)
Gandhi, Sonia (author)
Magdalinou, Nadia K (author)
Chen, Serene W (author)
Devine, Michael J (author)
Tosatto, Laura (author)
Kjaergaard, Magnus (author)
Beckwith, Joseph S (author)
Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe (author)
Iljina, Marija (author)
Cremades, Nunilo (author)
Dobson, Christopher M (author)
Wood, Nicholas W (author)
Klenerman, David (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

In:ACS chemical neuroscience: American Chemical Society (ACS)16;7:3, s. 399-4061948-7193

By the author/editor: Horrocks, Mathew ...; Lee, Steven F; Gandhi, Sonia; Magdalinou, Nadi ...; Chen, Serene W; Devine, Michael ...; show more...; Tosatto, Laura; Kjaergaard, Magn ...; Beckwith, Joseph ...; Zetterberg, Henr ...; Iljina, Marija; Cremades, Nunilo; Dobson, Christop ...; Wood, Nicholas W; Klenerman, David; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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