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

Horrocks, 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. (Universidad de Zaragoza) ; Dobson, C.M. ; Wood, N.W. ; Klenerman, D.

Resumen: 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.

Idioma: Inglés

DOI: 10.1021/acschemneuro.5b00324

Año: 2016

Publicado en: ACS CHEMICAL NEUROSCIENCE 7, 3 (2016), 399-406
ISSN: 1948-7193

Factor impacto JCR: 3.883 (2016)

Categ. JCR: CHEMISTRY, MEDICINAL rank: 7 / 60 = 0.117 (2016) - Q1 - T1
Categ. JCR: NEUROSCIENCES rank: 72 / 258 = 0.279 (2016) - Q2 - T1
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 85 / 287 = 0.296 (2016) - Q2 - T1

Factor impacto SCIMAGO: 1.538 - Medicine (miscellaneous) (Q1) - Biochemistry (Q1) - Physiology (Q1) - Cell Biology (Q2) - Cognitive Neuroscience (Q2)

Tipo y forma: Article (Published version)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)