Preparation and in vitro activity of single chain antibodies against Alzheimer's disease

Disease-modifying passive immunotherapies focused on reducing amyloid-beta (Aβ) deposition are a potential therapeutic strategy for Alzheimer's disease (AD). However, the results of Aβ passive immunotherapy clinical trials were unsatisfactory, largely due to the low efficacy of whole antibodies due to their relatively large molecular weight and low blood-brain barrier transmittance. Furthermore, the constant region fragments of whole antibodies can trigger inflammatory reactions, which raises safety concerns. Single chain fragment variables (scFvs), containing only the variable region of the heavy and light chains of antibodies, show great potential for the treatment of AD. With the aim of generating a safe and effective AD passive immunotherapy, we designed and successfully prepared scFvs targeting Aβ and investigated their activity in vitro. The results showed that both the 10D5-scFv and 12B4-scFv have high affinities for Aβ monomers, oligomers, and fibers. Moreover, scFvs could prevent the formation of Aβ oligomers and fibers, and block their cellular toxicity. In addition, 10D5-scFv and 12B4-scFv could bind to Aβ plaques on the sections of mice brains in the in vitro study, indicating potential for the treatment of AD.