Conformation-specific antibodies against multiple amyloid protofibril species from a single amyloid immunogen.

ABSTRACT: We engineered and employed a chaperone-like amyloid-binding protein Nucleobindin 1 (NUCB1) to stabilize human islet amyloid polypeptide (hIAPP) protofibrils for use as immunogen in mice. We obtained multiple monoclonal antibody (mAb) clones that were reactive against hIAPP protofibrils. A secondary screen was carried out to identify clones that cross-reacted with amyloid beta-peptide (Aβ42) protofibrils, but not with Aβ40 monomers. These mAbs were further characterized in several in vitro assays, in immunohistological studies of a mouse model of Alzheimer's disease (AD) and in AD patient brain tissue. We show that mAbs obtained by immunizing mice with the NUCB1-hIAPP complex cross-react with Aβ42, specifically targeting protofibrils and inhibiting their further aggregation. In line with co

SUBMITTER: Bonito-Oliva A 

PROVIDER: S-EPMC6378190 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature