Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease

Amyloid-beta (A beta) oligomers have emerged as the most toxic species in Alzheimer's disease (AD) and other amyloid pathologies. Also, A beta-42 peptide is more aggregation-prone compared to other A beta isoforms. Thus, we synthesized a small peptide of repeated sequence containing the last three amino acids, Val-40, Ile-41, and Ala-42 of A beta-42 that was subsequently aggregated and used to generate a novel antibody, VIA. In this study, we examined human AD and Tg2576 mouse brain samples using VIA in combination with other amyloid-specific antibodies and confirmed the specificity of VIA to oligomeric A beta-42. Moreover, we found that VIA does not recognize classic amyloid plaques composed of fibrillar A beta or A beta-40 ex vivo. Since VIA recognizes a distinct epitope specific to A beta-42 oligomers, it may have broad use for examining the accumulation of these oligomers in AD and other neurodegenerative diseases. VIA may also be used in immunotherapy studies to prevent neurodegenerative effects associated with A beta-42 oligomers.