Abstract

Recent advances in our understanding of the neurobiology of Alzheimer's disease (AD) have led to the development of putative disease-modifying treatments. The most revolutionary of these approaches consists in the removal of brain β-amyloid (Aβ) via anti-Aβ antibodies. Brain imaging and neuropathological studies have shown the ability of both active and passive anti-Aβ immunotherapies of clearing Aβ deposits from the brain of the AD patients. An active anti-Aβ vaccine preparation, AN1792, has been used in AD patients with some clues of clinical efficacy but causing meningoencephalitis in about 6% of patients and it has been abandoned. Several 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 the AD patients. The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-Aβ monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce Aβ burden in the brain of AD patients. However, the preliminary cognitive efficacy of bapineuzumab appears uncertain. The occurrence of vasogenic edema, especially in apolipoprotein E 4 carriers, may limit its clinical use and have led to abandon the highest dose of the drug (2 mg/kg). The results of four ongoing large Phase III trials on bapineuzumab will tell us if passive anti-Aβ immunization is able to alter the course if this devastating disease.