23. Soluble β-Amyloid Oligomer Formation and aggregation.

GA CANZIANI, A BAKER, S JUNG, H JIANG, M BRIGHAM-BURKE.

New Brunswick, NJ, USA

Simposio; Johnson&Johnson Bionalytical Symposium; 2005

Johnson&Johnson

The major protein component of amyloids associated with Alzheimer’s disease is a self-associating peptide, 40-42 residues long, known as Aβ generated by the proteolytic processing of the amyloid precursor protein (APP) by neurons. Because amyloid oligomers are toxic and promote fibrillary tangle growth they have been directly implicated in Alzheimer’s pathology and have become ideal targets for immune therapy. However, time-dependent size, folding, and solubility changes of this antigen are major challenges for product development. Applying size exclusion chromatography and gel electrophoresis it was possible to characterize the time and temperature dependent formation and stability of oligomers formed from monomeric preparations of synthetic analogues of native 38, 40, and 42 residue Aβ. To resolve the conformational changes and residue accessibility associated with Aβ monomers and each of the oligomeric states SPR binding assays were developed using a set of non-conformational antibodies, previously generated via peptide-fragment immunization.