In situ measurements of the formation and morphology of intracellular beta-amyloid fibrils by super-resolution fluorescence imaging

GABRIELE S. KAMINSKI SCHIERLE; SEBASTIAN VAN DE LINDE; MIKLOS ERDELYI; ELIN K. ESBJORNER; TERESA KLEIN; ERIC REES; CARLOS W. BERTONCINI; CHRISTOPHER M. DOBSON; MARKUS SAUER; CLEMENS F. KAMINSKI

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2011 vol. 133 p. 12902 - 12905

0002-7863

Misfolding and aggregation of peptides and proteins is a characteristic of many neurodegenerative disorders, including Alzheimer´s disease (AD). In AD the beta-amyloid peptide (Abeta) aggregates to form characteristic fibrillar structures, which are the deposits found as plaques in the brains of patients. We have used direct stochastic optical reconstruction microscopy, dSTORM, to probe the process of in situ Abeta aggregation and the morphology of the ensuing aggregates with a resolution better than 20 nm. We are able to distinguish different types of structures, including oligomeric assemblies and mature fibrils, and observe a number of morphological differences between the species formed in vitro and in vivo, which may be significant in the context of disease. Our data support the recent view that intracellular Abeta could be associated with Abeta pathogenicity in AD, although the major deposits are extracellular, and suggest that this approach will be widely applicable to studies of the molecular mechanisms of protein deposition diseases.