Recent advance in immunotherapies for Alzheimer disease With special reference to DNA vaccination

Alzheimer disease (AD) is the most common cause of dementia characterized by progressive neurodegeneration. Based on the amyloid cascade hypothesis, several immunotherapies for AD have been developed as curative treatment. In 1999, Schenk et al. reported for the first time that amyloid beta (A beta) deposits in AD model mice could be reduced by active vaccination with A beta peptide. Although clinical trials with the A beta peptide were halted due to the development of meningoencephalitis in some treated patients, the vaccine therapy was judged to be effective on the basis of clinical and pathological analyses. Passive immunization using humanized anti-A beta monoclonal antibodies is also under clinical trials; however they have some problems to be solved. As other strategies, DNA vaccines have been developed as immunotherapies for AD, which is simple, easily modified and can be administered without adjuvant. DNA vaccines were developed by several groups including our laboratory, which induced A beta reduction in AD model mice without side effects. DNA vaccination may be open up new avenue of vaccine therapies for AD in the near future.