Biochemical and Biophysical Research Communications, Vol.394, No.2, 393-397, 2010
Design and development of non-fibrillar amyloid beta as a potential Alzheimer vaccine
Alzheimer's disease (AD) is the most common cause of dementia affecting the elderly. Treatment for effective cure of this complex neurodegenerative disease does not yet exist. In AD, otherwise soluble, monomeric form of amyloid beta (A beta) peptide converts into toxic, fibrillar form rich in beta-sheet content. Several immunological approaches that prevent this conversion of A beta into pathological form or that accelerate its clearance are being actively pursued worldwide. As part of these attempts, we report here, the design and characterization of a non-amyloidogenic homologue of A beta (A beta-KEK). We demonstrate that this peptide is helical in nature and retains the immunoneutralizing epitopes of native A beta. More importantly, Fab fragments of the polyclonal anti-A beta-KEK antibodies interfere with formation of A beta fibrils as well as dissociate the preformed A beta aggregates in vitro. These results suggest that non-amyloidogenic A beta-KEK may serve as a safer alternative vaccine for Alzheimer's disease. (C) 2010 Elsevier Inc. All rights reserved.