Design and development of non-fibrillar amyloid β 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 β (Aβ) peptide converts into toxic, fibrillar form rich in β-sheet content. Several immunological approaches that prevent this conversion of Aβ 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 Aβ (Aβ-KEK). We demonstrate that this peptide is helical in nature and retains the immunoneutralizing epitopes of native Aβ. More importantly, Fab fragments of the polyclonal anti-Aβ-KEK antibodies interfere with formation of Aβ fibrils as well as dissociate the preformed Aβ aggregates in vitro. These results suggest that non-amyloidogenic Aβ-KEK may serve as a safer alternative vaccine for Alzheimer’s disease.