DNA Vaccination Target on Amyloid Oligomer also Reduce tau Pathology and Improve Synaptic Function in Aged 3xTg-AD Mice

Abstract

Background: Active immunotherapy has been widely used as a potential therapeutic method for both treatment and prevention of Alzheimer’s disease (AD). Amyloid deposition and tau hyperphosphorylation are main pathological hallmarks of AD. Reduction in both is required to regulate synaptic proteins neurotransmission which can finally protect cognitive function. Growing evidence suggests that the most toxic β-Amyloid peptide (Aβ) oligomers can be detected from the very beginning of AD development, so it is wise for us to develop effective therapy method focus on Aβ oligomers rather than monomers. Methods: The 3×Tg-AD mice were randomly divided into two groups immunized with p(Aβ3–10)10-MT and PBS respectively. The PBS group was used for positive group while C57/B6 mice was used for negative group. ELISA was used to detect the antibody titers and Morris Water Maze was to analysis the cognitive function. The Aβ ,Tau hyperphosphorylation, Neuron and synaptic protein were detected through immunohistochemistry and western blot. Results: Mice immunized with p(Aβ3–10)10-MT can not only reduce the levels of Aβ oligomers and plaque deposits but also protect neuron as well as synaptic function, finally prevent the decline spatial memory in transgenic mice. Conclusions: Our novel DNA genetic vaccine is highly safe and effective, thus providing strong evidence for the treatment and prevention of early AD.