Reduction of cerebral Aβ burden and improvement in cognitive function in Tg-APPswe/PSEN1dE9 mice following vaccination with a multivalent Aβ3-10 DNA vaccine.

To develop a safe and efficient Aβ vaccine for Alzheimer's disease, we constructed a plasmid DNA vaccine encoding ten repeats of Aβ3-10 and three copies of C3d-p28 as a molecular adjuvant and administered it intramuscularly in 12-month-old female Tg-APPswe/PSEN1dE9 mice. Therapeutic immunization with p(Aβ3-10)10-C3d-p28.3 stimulated a Th2 immune response that elicited therapeutic levels of anti-Aβ antibodies and improved cognitive function. In addition, the vaccine reduced the cerebral Aβ burden and astrocytosis without increasing the incidence of microhemorrhage. Our results indicate that the p(Aβ3-10)10-C3d-p28.3 vaccine is a promising immunotherapeutic option for Aβ vaccination in Alzheimer's disease.