Abstract
Disease-modifying passive immunotherapies focusing on removal of abnormal phosphorylated Tau (p-Tau) constitute promising treatments for Alzheimer's disease (AD). Although several prior immunotherapies targeting p-Tau appear to be beneficial against AD, they have limitations such as the low blood-brain barrier (BBB) penetration rate, short half-life of antibodies, and the likelihood of inflammation. To address these issues, we designed a novel immunotherapy for AD. To this end, a single chain antibody (scFv) targeting p-Tau was generated, and a recombinant adeno-associated virus that can cross the BBB (rAAV/BBB) was used as a vector to express scFv for at least 22 weeks in the mouse brain. Results showed that the scFv constructed in this study had a high affinity to p-Tau and could bind to neuronal tangles in the section of brains of AD model mice. Moreover, the rAAV/BBB could cross the BBB, infect neuronal cells, and express scFv. This novel immunotherapy could effectively deliver scFv into the brain and resulted in a continuous expression of scFv in vivo, suggesting its potential for the treatment of AD.
NSTL
Elsevier