Clinical trials of amyloid-based immunotherapy for Alzheimer's disease: end of beginning or beginning of end?

INTRODUCTION: Amyloid deposit and hyperphosphorylated Tau protein contribute to pathological changes seen in Alzheimer's disease (AD) and imply that removal may reverse the cognitive decline. Immunotherapy is a potential way of reducing the load of amyloid or Tau in the brain. AREAS COVERED: This review summarizes recent clinical trials that have investigated immunotherapy to treat AD and its potential mechanisms. In addition, the potential opportunities as well as challenges of immunotherapy for AD in clinical trials are also discussed. EXPERT OPINION: Amyloid-based immunotherapy for AD is a novel method with potential; however, some clinical trials were terminated because of the adverse effects. Further studies need to determine the following questions: (i) which is better, passive, or active immunotherapy; (ii) which could be used for the vaccine, amyloid or Tau; (iii) which is better, short- or long-antigen vaccine; and (iv) the route of delivery for antigen or antibody.