EFFECT OF ACID PREDISSOLUTION ON FIBRIL SIZE AND FIBRIL FLEXIBILITY OF SYNTHETIC BETA-AMYLOID PEPTIDE

beta-amyloid peptide (A beta) is the major protein component of senile plaques and cerebrovascular amyloid deposits in Alzheimer's patients. Several researchers have demonstrated that A beta is neurotoxic in in vitro and in vivo systems. Peptide aggregation state and/or conformat ion might play a significant role in determining the toxicity of the p eptide. The size and flexibility of fibrils formed from the synthetic peptide beta(1-39), corresponding to the first 39 residues of A beta, were determined. Samples were prepared either directly from lyophilize d peptide or diluted from a 10 mg/ml stock solution in 0.1% trifluoroa cetic acid (TFA). All samples had a final peptide concentration of 0.5 mg/ml, a final pH of 7.4, and a final NaCl concentration of 0.14 M. T he molecular weight and linear density of the fibrils increased with i ncreasing pre-incubation time in TFA, based on static light scattering measurements. Analysis of the angular dependence of the intensity of scattered light indicated that the fibrils were semi-flexible chains a nd that the fibril flexibility decreased with increasing pre-incubatio n time in TFA. There was a concomitant change in phase behavior from p recipitation to gelation with the decrease in fibril flexibility.