Ultrastructural evidence for self-replication of Alzheimer-associated Aβ42 amyloid along the sides of fibrils

• DOI: 10.1073/pnas.1918481117
• Publication Date: 2020-05-22T00:07:50Z
• Authors: Mattias Törnquist; Risto Cukalevski; Ulrich Weininger; Georg Meisl; Tuomas P. J. Knowles; Thom Leiding; Anders Malmendal; Mikael Akke; Sara Linse
• Keywords: Autocatalysis; Amyloid (mycology); Cryo-Electron Microscopy

The nucleation of Alzheimer-associated Aβ peptide monomers can be catalyzed by preexisting fibrils. This leads to autocatalytic amplification aggregate mass and underlies self-replication generation toxic oligomers associated with several neurodegenerative diseases. However, the nature interactions between monomeric species fibrils during this key process, indeed ultrastructural localization interaction sites have remained elusive. Here we used NMR optical spectroscopy identify conditions that enable capture transient aggregation secondary Aβ42 peptide. Cryo-electron microscopy (cryo-EM) images show new aggregates protrude from entire length progenitor fibril. These protrusions are morphologically distinct well-ordered dominating at end process. data provide direct evidence through occurs along sides fibrils, which become heavily decorated under current solution (14 µM Aβ42, 20 mM sodium phosphate, 200 EDTA, pH 6.8).