Amyloidogenicity and toxicity of the reverse and scrambled variants of amyloid‐β 1‐42

摘要

β‐amyloid 1‐42 (Aβ1‐42) is a self‐assembling peptide that goes through many conformational and morphological changes before forming the fibrils that are deposited in extracellular plaques characteristic of Alzheimer's disease. The link between Aβ1‐42 structure and toxicity is of major interest, in particular, the neurotoxic potential of oligomeric species. Many studies utilise reversed (Aβ42‐1) and scrambled (AβS) forms of amyloid‐β as control peptides. Here, using circular dichroism, thioflavin T fluorescence and transmission electron microscopy, we reveal that both control peptides self‐assemble to form fibres within 24 h. However, oligomeric Aβ reduces cell survival of hippocampal neurons, while Aβ42‐1 and Aβs have reduced effect on cellular health, which may arise from their ability to assemble rapidly to form protofibrils and fibrils.