Is there still any hope for amyloid-based immunotherapy for Alzheimer's disease?

Curr Opin Psychiatry. 2014 Mar;27(2):128-37. doi: 10.1097/YCO.0000000000000041.


Purpose of review: We reviewed clinical trials on active and passive anti-β-amyloid (Aβ) immunotherapy for the treatment of Alzheimer's disease with a particular focus on monoclonal antibodies against Aβ.

Recent findings: Studies on anti-Alzheimer's disease immunotherapy published in the period from January 2012 to October 2013 were reviewed.

Summary: Both active and passive anti-Aβ immunotherapies were shown to clear brain Aβ deposits. However, an active anti-Aβ vaccine (AN1792) has been discontinued because it caused meningoencephalitis in 6% of Alzheimer's disease patients treated. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients with bapineuzumab, a humanized monoclonal antibody directed at the N-terminal sequence of Aβ, were disappointing. Another antibody, solanezumab, directed at the mid-region of Aβ, failed in two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients. A third Phase III study with solanezumab is ongoing in mildly affected Alzheimer's disease patients based on encouraging results in this subgroup of patients. Second-generation active Aβ vaccines (ACC-001, CAD106, and Affitope AD02) and new passive anti-Aβ immunotherapies (gantenerumab and crenezumab) are being tested in prodromal Alzheimer's disease patients, in presymptomatic individuals with Alzheimer's disease-related mutations, or in asymptomatic individuals at risk of developing Alzheimer's disease to definitely test the Aβ cascade hypothesis of Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / immunology
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / immunology
  • Amyloid beta-Peptides / therapeutic use*
  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Humans
  • Immunotherapy / methods*


  • Amyloid beta-Peptides
  • Antibodies, Monoclonal