Not Oligomers but Amyloids are Cytotoxic in the Membrane-Mediated Amyloidogenesis of Amyloid- Peptides

The formation of neurotoxic aggregates by amyloid- peptide (A) is considered to be a key step in the onset of Alzheimer's disease. It is widely accepted that oligomers are more neurotoxic than amyloid fibrils in the aqueous-phase aggregation of A. Membrane-mediated amyloidogenesis is also relevant to the pathology, although the relationship between the aggregate size and cytotoxicity has remained elusive. Here, aggregation processes of A on living cells and cytotoxic events were monitored by fluorescence techniques. A formed amyloids after forming oligomers composed of approximate to 10 A molecules. The formation of amyloids was necessary to activate apoptotic caspase-3 and reduce the ability of the cell to proliferate; this indicated that amyloid formation is a key event in A-induced cytotoxicity.