Peripherally administered sera antibodies recognizing amyloid-β oligomers mitigate Alzheimer's disease-like pathology and cognitive decline in aged 3× Tg-AD mice.

摘要: Active and passive immunotherapy targeting amyloid-β (Aβ) may be the most promising strategy to prevent or treat Alzheimer's disease (AD). Previously, immunization with recombinant 6Aβ15-T antigen generated robust anti-Aβ serum antibodies that strongly recognized Aβ42 oligomers in different mice, markedly reduced amyloid burden, improved behavioral performance of immunized older AD mice. Here, we further determined these anti-6Aβ15-T from strains mice displayed antibody responses against same epitopes Aβ1-15 region. Peripheral administration was also effective mitigate AD-like pathology cognitive decline aged 3× Tg-AD Specifically, levels Aβ tau brains were significantly after immunotherapy, which seemed necessary beneficial ameliorate memory impairment. In addition, our results showed this prevented presynaptic dynamin 1 degradation, might help protect synaptic functions allow functional recovery cognition. Moreover, rabbits induced a similar response as rabbit reacted inhibited oligomer-mediated neurotoxicity. We concluded oligomer conformation-sensitive is providing potentially therapeutic effects by reducing tau.