Vadukul, Devkee M, Vrancx, Céline, Burguet, Pierre, Contino, Sabrina, Suelves, Nuria, Serpell, Louise C, Quinton, Loïc and Kienlen-Campard, Pascal (2021) An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β. Scientific Reports, 11 (1). a11570 1-17. ISSN 2045-2322

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Abstract

A key hallmark of Alzheimer’s disease is the extracellular deposition of amyloid plaques composed primarily of the amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide is a product of sequential cleavage of the Amyloid Precursor Protein, the first step of which gives rise to a C-terminal Fragment (C99). Cleavage of C99 by γ-secretase activity releases Aβ of several lengths and the Aβ42 isoform in particular has been identified as being neurotoxic. The misfolding of Aβ leads to subsequent amyloid fibril formation by nucleated polymerisation. This requires an initial and critical nucleus for self-assembly. Here, we identify and characterise the composition and self-assembly properties of cell-derived hexameric Aβ42 and show its assembly enhancing properties which are dependent on the Aβ monomer availability. Identification of nucleating assemblies that contribute to self-assembly in this way may serve as therapeutic targets to prevent the formation of toxic oligomers.

Item Type:	Article
Schools and Departments:	School of Life Sciences > Neuroscience
SWORD Depositor:	Mx Elements Account
Depositing User:	Mx Elements Account
Date Deposited:	17 Aug 2021 09:30
Last Modified:	17 Aug 2021 10:00
URI:	http://sro.sussex.ac.uk/id/eprint/101166

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