Central amyloid--specific single chain variable fragment ameliorates A aggregation and neurotoxicity

Anti-amyloid- immunotherapies are a promising therapeutic approach for the treatment and prevention of Alzheimers disease (AD). Single chain antibody fragments (scFv) are an attractive alternative to whole antibodies due to their small size, single polypeptide format and inability to stimulate potentially undesirable Fc-mediated immune effector functions. We have generated the scFv derivative of anti-A monoclonal antibody, 1E8, known to target residues 1722 of A. Here we show that the soluble 1E8 scFv binds to the central region of A with an affinity of 55 nM and significantly reduces fibril formation of A(142). Furthermore, 1E8 scFv ameliorates A(142)-mediated toxicity in the PC12 cell line and murine primary neuronal cultures. This ability to both target the central region of A and prevent A(142) neurotoxicity in vitro makes it a promising therapeutic antibody building block for further functionalization, toward the treatment of AD.