N-Terminal Truncated Pyroglutamyl β Amyloid Peptide Aβpy3-42 Shows a Faster Aggregation Kinetics than the Full-Length Aβ1-42

We tested directly the differences in the aggregation kinetics of three important beta amyloid peptides, the full-length A beta 1-42, and the two N-terminal truncated and pyroglutamil modified A beta py3-42 and A beta py11-42 found in different relative concentrations in the brains in normal aging and in Alzheimer disease. By following the circular dichroism signal and the ThT fluorescence of the solution in phosphate buffer, we found substantially faster aggregation kinetics for A beta py3-42. This behavior is due to the particular sequence of this peptide, which is also responsible or the specific oligomeric aggregation states, found by TEM, during the fibrillization process, which are very different from those of A beta 1-42, more prone to fibril formation. In addition, A beta py3-42 is found here to have an inhibitory effect on A beta 1-42 fibrillogenesis, coherently with its known greater infective power. This is an indication of the important role of this peptide in the aggregation process of beta-peptides in Alzheimer disease. (C) 2009 Wiley Periodicals, Inc. Biopolymers 91: 861-873, 2009.