Amyloidogenicity and toxicity of the reverse and scrambled variants of amyloid-beta 1-42

摘要

beta-amyloid 1-42 (A beta 1-42) 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 A beta 1-42 structure and toxicity is of major interest, in particular, the neurotoxic potential of oligomeric species. Many studies utilise reversed (A beta 42-1) and scrambled (A beta S) forms of amyloid-beta 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 A beta reduces cell survival of hippocampal neurons, while A beta 42-1 and Abs have reduced effect on cellular health, which may arise from their ability to assemble rapidly to form protofibrils and fibrils.