75425 20200221144305.0 doi 10.1021/acschemneuro.5b00324 sideral 107780 ART-2016-107780 eng Horrocks, M.H. Single-molecule imaging of individual amyloid protein aggregates in human biofluids 2016 Access copy available to the general public Unrestricted 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 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. info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.883 2016 CHEMISTRY, MEDICINAL 7 / 60 = 0.117 2016 Q1 T1 NEUROSCIENCES 72 / 258 = 0.279 2016 Q2 T1 BIOCHEMISTRY & MOLECULAR BIOLOGY 85 / 287 = 0.296 2016 Q2 T1 1.538 2016 Medicine (miscellaneous) 2016 Q1 Biochemistry 2016 Q1 Physiology 2016 Q1 Cell Biology 2016 Q2 Cognitive Neuroscience 2016 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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. (orcid)0000-0002-9138-6687 Cremades, N. Universidad de Zaragoza Dobson, C.M. Wood, N.W. Klenerman, D. 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 7, 3 (2016), 399-406 ACS CHEMICAL NEUROSCIENCE ACS CHEMICAL NEUROSCIENCE 1948-7193 3247542 http://zaguan.unizar.es/record/75425/files/texto_completo.pdf Versión publicada 111073 http://zaguan.unizar.es/record/75425/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:75425 articulos driver 2020-02-21-13:34:35 ARTICLE