An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β

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