Abstract

In the last decade, new therapeutic approaches targeting β-amyloid (Aβ) have been discovered and developed with the hope of modifying the natural history of Alzheimer's disease (AD). The most revolutionary of these approaches consists in the removal of brain Aβ via anti-Aβ antibodies. After an active vaccine (AN1792) was discontinued in 2002 due to occurrence of meningoencephalitis in approximately 6% of patients, several other second-generation active Aβ vaccines and passive Aβ immunotherapies have been developed and are under clinical investigation with the aim of accelerating Aβ clearance from the brain of AD patients. The most advanced of these immunological approaches is bapineuzumab, which is composed of humanized anti-Aβ monoclonal antibodies that has been tested in two Phase II trials. Bapineuzumab has been shown to reduce Aβ burden in the brain of AD patients. However, its preliminary cognitive efficacy appears uncertain, particularly in ApoE ε4 carriers, and vasogenic edema may limit its clinical use. The results of four ongoing large Phase III trials on bapineuzumab will provide answers regarding whether passive anti-Aβ immunization is able to alter the course of this devastating disease.