Alzheimer's disease is a neurodegenerative disease that affects many patients worldwide. The amyloid cascade hypothesis has been adopted by most researchers as the mechanism underlying Alzheimer's disease. Aβ plaques have been considered the core factor in the neurotoxic effect in Alzheimer's disease, though some controversy remains. Further effort is necessary to elucidate the mechanism and to develop effective treatments. Previous studies have indicated that eliminating Aβ plaques could improve synaptic plasticity and cognitive function. Researchers have developed various forms of vaccines to prevent Aβ deposition or eliminate Aβ plaques and have made some progress. We developed a new vaccine, Aβ3-10-KLH, to increase the level of the anti-Aβ immune response, and we show that this vaccine resulted in a sustained prevention of Aβ deposition at 4 months after cessation of the vaccine treatment. At the same time point, the expression of synaptophysin and NMDAR2B in APP/PS1 transgenic mice was increased by immunization.