Alzheimer's disease (AD) is the most common cause of dementia with very few drugs available for its treatment. In 1999, Schenk et al reported that Abeta 1-42 peptide vaccination in AD model mice causes the reduction in Abeta deposits. Thereafter, a vaccine therapy was developed for the curative treatment of AD. Clinical trials of active vaccination for AD patients were halted due to the development of meningoencephalitis in some patients; however, vaccine therapy is thought to be effective based on the clinical and pathological findings of the vaccinated patients. Based on this information, active and passive vaccines have been developed, some of which are now urdergoing clinical trials in Europe and USA. However, there are still some problems for general application of such drugs for AD patients. Recently, we developed nonviral DNA vaccines and used them to obtain a substantial Abeta reduction in AD model mice without any side effects. In this article, we will review conventional vaccine therapies and introduce our non-viral DNA vaccine therapy. Finally, we will present data regarding the mechanisms of Abeta reduction after DNA vaccination. DNA vaccination for AD may open up new avenues in vaccine therapy for the treatment of AD.