AGGREGATION STATE AND NEUROTOXIC PROPERTIES OF ALZHEIMER BETA-AMYLOIDPEPTIDE

The behaviour of synthetic batches of beta-amyloid (beta A) 1-40 pepti de in solution has been studied. The effects of beta A1-40 on a PC12 c ell toxicity assay was dependent upon the time of preincubation of an aqueous solution of the peptide before application to the cells. Fibri llization of the beta A1-40, quantitatively assessed by the binding of Congo red to amyloid fibrils, also increased in a time dependent mann er over the 168 h incubation period studied. The degree of Congo red b inding, in the absence of any preincubation, differed between two synt hetically distinct batches of the peptide. The rate of development of fibril formation during subsequent incubation also differed between th e two batches and appeared to parallel the effects on cell viability. Infra-red spectroscopic analysis revealed beta-sheet formation for bot h batches and other more subtle conformational differences between the peptides. Electron microscope examination of the batches of beta A1-4 0 confirmed the difference in occurrence and development of fibrils. A t high magnification, fibrils of both batches exhibited a helical stru cture. The results suggest that the development of neurotoxicity of be ta A1-40 is related to the fibrillar state of the peptide.