Comparative Analysis of Human and Dutch-Type Alzheimer β-Amyloid Peptides by Infrared Spectroscopy and Circular Dichroism

Abstract

The 42 amino acid βA4 peptide is the major constituent of the senile plaques, one of the hallmark neuropathological lesions of Alzheimer′s disease. While C-terminally truncated variants were shown to be present in normal body fluids, a single Glu → Gln change in the 39 amino acid form of βA4 results in accelerated fibril formation in the brains of patients with Dutch-type hereditary cerebral hemorrhage with amyloidosis. In this study we used Fourier-transform infrared and circular dichroism spectroscopies on synthetic peptides to demonstrate that this mutation results in altered secondary structure in membrane mimicking solvents, characterized by a considerably higher β-structure content for the mutant peptide. Moreover, extreme high and low pH were less effective in eliminating the β-conformation for the Dutch-variant than for the normal human sequence.