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


METHODS
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.


CONCLUSIONS
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.
Nanjing University School of Medicine, Jinling Hospital, Department of Neurology , 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province , China +86 25 8480 1861 ; +86 25 8480 5169 ; jiangyjnju@gmail.com.
Yun
Y
Li
Yahong
Y
Liu
Zhaojun
Z
Wang
Yongjun
Y
Jiang
D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D000682:Amyloid / Q000032:analysis / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000627:therapeutic use; D000918:Antibody Specificity; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D006801:Humans; D007114:Immunization / Q000009:adverse effects / Q000379:methods; D007116:Immunization, Passive / Q000009:adverse effects / Q000379:methods; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D016233:Immunotherapy, Active / Q000009:adverse effects / Q000379:methods; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000276:immunology; D010951:Plasma Exchange; D010956:Plasmapheresis; D011499:Protein Processing, Post-Translational; D016032:Randomized Controlled Trials as Topic; D016875:tau Proteins / Q000276:immunology / Q000378:metabolism
C437846:AN-1792; D023582:Alzheimer Vaccines; D000682:Amyloid; D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C054369:MAPT protein, human; D016875:tau Proteins; C571128:gantenerumab; C550616:solanezumab; C545458:bapineuzumab