The use of antibodies against the Aß peptide to remove amyloid from the brain has advanced to the stage of clinical testing in patients. However, the mechanisms by which antibodies might act to remove amyloid are not well understood. One such mechanism involves a possible catalytic function of antibodies to modify the conformation of the Aß peptide to one that is less able to form aggregates. One attraction of this proposed mechanism is the fact that it can function at stoichiometries less than unity. Using Attenuated Total Reflection Fourier Transform InfraRed (ATR-FTIR) spectroscopy we have previously measured a number of conformational changes that Aß peptides undergo when forming different types of aggregates (i.e., monomers, oligomers, and fibrils). These conformations have also been corroborated by physical visualization of their microscopy topology by Atomic Force Microscopy, AFM. We have examine how antibodies against Aß modify the process of aggregate formation, the corresponding changes in conformation, and the time-lines related to the antibody- Aß interactions. By studying the effects of amyloid peptides with 40, 42 amino acid sequences, both separated or combined, it will allow one to understand the effects of length and end group of the peptide.

The long-term application of this work is to identify the extent to which antibodies can modify Aß secondary structure and determine what the impact of this mechanism of fibril dissolution might be in relation to other mechanisms in mouse models and patients.