Improving memory and decreasing cognitive impairment in Tg-APPswe/PSEN1dE9 mice with Aβ3-10 repeat fragment plasmid by reducing Aβ deposition and inflammatory response

The present study aimed to investigate the effects of Aβ3-10 repeat fragment plasmid for the treatment of Tg-APPswe/PSEN1dE9 (Tg) mice. The plasmid pcDNA3.1-(Aβ3-10)10-CpG was constructed and intramuscularly injected into 12-month-old Tg mice. Through the use of behavioral tests, anti-Aβ antibody and Aβ assays, cytokine assay, Aβ deposition, and astrocytes analysis results demonstrated that Aβ3-10 repeat fragment plasmid exhibited immunogenicity and reduced memory impairment in Tg mice via clearance of cerebral Aβ deposition, without significant side effects. Aβ3-10 repeat fragment plasmid immunization reduced Th1 cell-mediated immunity, secretion of interferon-γ, and stimulation to astrocytes. These data showed that the Aβ3-10 repeat fragment plasmid improved memory and decreased cognitive impairment in Tg mice by reducing Aβ deposition and inflammatory responses.

Research highlights► We constructed a new plasmid pcDNA3.1-(Aβ3-10)10-CpG for the therapy of AD. ► The plasmid intramuscularly injected reduced memory impairment in Tg mice. ► The plasmid immunization reduced cerebral Aβ deposition and inflammatory response.