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 (Abeta) peptide converts into toxic, fibrillar form rich in beta-sheet content. Several immunological approaches that prevent this conversion of Abeta 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 Abeta (Abeta-KEK). We demonstrate that this peptide is helical in nature and retains the immunoneutralizing epitopes of native Abeta. More importantly, Fab fragments of the polyclonal anti-Abeta-KEK antibodies interfere with formation of Abeta fibrils as well as dissociate the preformed Abeta aggregates in vitro. These results suggest that non-amyloidogenic Abeta-KEK may serve as a safer alternative vaccine for Alzheimer's disease.
Subramanian
Sarada
S
Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Bangalore 560029, India. sarada@nimhans.kar.nic.in
Bandopadhyay
Debashree
D
Mishra
Pradeep Kumar
PK
Mathew
Maya
M
John
Mathew
M
D000544:Alzheimer Disease / Q000517:prevention & control*; D023582:Alzheimer Vaccines / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000276:immunology*; D000906:Antibodies / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D017433:Protein Structure, Secondary
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000906:Antibodies; D016056:Immunodominant Epitopes; D007140:Immunoglobulin Fab Fragments; D010455:Peptides