Alzheimer’s disease and immunotherapy: what is wrong with clinical trials?

Abstract

Alzheimer’s disease (AD) is characterized by progressive neurodegeneration and is the most common cause of dementia. Immunotherapy has recently been regarded as a potential treatment for AD. This stems from the fact that the clinical and pathological findings from the active AD vaccine trial suggests that such vaccine therapy may be effective for AD. However, this trial was halted because of the occurrence of meningoencephalitis in some patients. Avoiding excessive immune reaction is necessary for the success of vaccine therapy. For this purpose, adjuvant-free vaccine therapies (eg, passive immunization or DNA vaccines) are currently under investigation. However, the results of clinical trials employing both active and passive anti-amyloid-beta immunotherapy have been unsatisfactory. In this article, we will analyze the reasons for the limited efficacy of currently available immunotherapies and discuss the effectiveness of new vaccine therapies. Finally, we will speculate on the possibility of its clinical application.

Keywords:

• Aβ peptide vaccine
• amyloid-beta
• amyloid cascade theory
• immunotherapy
• monoclonal antibody
• tau

Disclosure

Yoh Matsumoto is an inventor of DNA vaccines. The authors report no other conflicts of interest in this work.