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

Purpose of reviewWe reviewed clinical trials on active and passive anti--amyloid (A) immunotherapy for the treatment of Alzheimer's disease with a particular focus on monoclonal antibodies against A.Recent findingsStudies on anti-Alzheimer's disease immunotherapy published in the period from January 2012 to October 2013 were reviewed.SummaryBoth active and passive anti-A immunotherapies were shown to clear brain A deposits. However, an active anti-A 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 A, were disappointing. Another antibody, solanezumab, directed at the mid-region of A, 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 A vaccines (ACC-001, CAD106, and Affitope AD02) and new passive anti-A 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 A cascade hypothesis of Alzheimer's disease.