The Properties of Amyloid-β Fibrils Are Determined by their Path of Formation

Journal of Molecular Biology
Kristoffer BrännströmAnders Olofsson

Abstract

Fibril formation of the amyloid-β peptide (Aβ) follows a nucleation-dependent polymerization process and is associated with Alzheimer's disease. Several different lengths of Aβ are observed in vivo, but Aβ1-40 and Aβ1-42 are the dominant forms. The fibril architectures of Aβ1-40 and Aβ1-42 differ and Aβ1-42 assemblies are generally considered more pathogenic. We show here that monomeric Aβ1-42 can be cross-templated and incorporated into the ends of Aβ1-40 fibrils, while incorporation of Aβ1-40 monomers into Aβ1-42 fibrils is very poor. We also show that via cross-templating incorporated Aβ monomers acquire the properties of the parental fibrils. The suppressed ability of Aβ1-40 to incorporate into the ends of Aβ1-42 fibrils and the capacity of Aβ1-42 monomers to adopt the properties of Aβ1-40 fibrils may thus represent two mechanisms reducing the total load of fibrils having the intrinsic, and possibly pathogenic, features of Aβ1-42 fibrils in vivo. We also show that the transfer of fibrillar properties is restricted to fibril-end templating and does not apply to cross-nucleation via the recently described path of surface-catalyzed secondary nucleation, which instead generates similar structures to those acquired via de novo p...Continue Reading

Citations

Oct 2, 2019·The FEBS Journal·Tohidul IslamAnders Olofsson
Nov 19, 2019·Frontiers in Aging Neuroscience·Puneet TalwarRachna Agarwal
Dec 18, 2019·PeerJ·Andrius SakalauskasVytautas Smirnovas
Nov 27, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Monica Gireud-GossAkihiko Urayama
Oct 15, 2020·International Journal of Molecular Sciences·Tomas SneiderisVytautas Smirnovas
May 4, 2021·Frontiers in Molecular Biosciences·Saeid Hadi AlijanvandAlexander K Buell

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