New developments of clinical trial in immunotherapy for Alzheimer's disease

Active or passive immunotherapy is expected to slow or stop the pathological process of Alzheimer's disease (AD). Immunotherapy for AD has demonstrated that targeting beta-amyloid (Aβ) or tau protein with vaccines or antibodies can reduce AD pathologies. Active anti-Aβ immunization for AD includes using AN1792 and second generation vaccines such as ACC-001, CAD106 and AFFITOPE vaccines, while antibodies for passive immunization include monoclonal antibodies and intravenous immunoglobulin (IVIG). Preclinical trials have shown powerful evidence of significant advances for more than a decade; however, there are still issues that need to be addressed in clinical trials. In the phase IIa AN1792 trial, 6% of patients who received the vaccination were diagnosed with meningoencephalitis as an adverse effect. There was a high incidence of amyloid-related imaging abnormalities (ARIA) in patients treated with some monoclonal antibodies. Moreover, several phase 3 clinical trial findings of immunization targeting Aβ were negative. These issues require attention in order to improve the safety and efficacy of immunization strategies in AD. Prevention studies and other novel immunization strategies have the potential to dramatically impact AD care. Herein we review the recent advances in clinical trials involving immunotherapy for AD.