doi:10.1021/acschemneuro.5b00324engHorrocks, M.H.Lee, S.F.Gandhi, S.Magdalinou, N.K.Chen, S.W.Devine, M.J.Tosatto, L.Kjaergaard, M.Beckwith, J.S.Zetterberg, H.Iljina, M.Cremades, N.Dobson, C.M.Wood, N.W.Klenerman, D.Single-molecule imaging of individual amyloid protein aggregates in human biofluidsART-2016-107780The 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 a-synuclein, tau, and amyloid-ß. 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.2016http://zaguan.unizar.es/record/7542510.1021/acschemneuro.5b00324http://zaguan.unizar.es/record/75425oai:zaguan.unizar.es:75425ACS CHEMICAL NEUROSCIENCE 7, 3 (2016), 399-406byhttp://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccess