Setback for an Alzheimer’s disease vaccine

In 1907, Alois Alzheimer described the pathologic hallmarks of the neurodegenerative disease that now carries his name: the extracellular β-amyloid plaque and the intracellular neurofibrillary tangle. Following the identification in the mid-1980s of the small peptide Aβ as the primary constituent of β-amyloid plaques1,2⇓ and the later understanding that inherited forms of early-onset Alzheimer disease (AD) alter Aβ metabolism and promote β-amyloid accumulation,3 treatments targeting Aβ and β-amyloid have been aggressively pursued. In this issue of Neurology , Orgogozo et al. report on the phase II trial of one anti-Aβ therapy, Aβ immunization, and the details of the meningoencephalitis-related complications that developed in 6% of the patients.4

Anti-Aβ immunotherapy for AD has been the subject of intense investigation since Schenk et al. demonstrated in 1999 that active immunization with Aβ reduces β-amyloid burden in a transgenic mouse model.5 Subsequent work, including the finding that Aβ immunization was associated with improved spatial cognition in β-amyloid-depositing mice,6,7⇓ indicated that Aβ immunization, and even passive transfer of anti-Aβ antibodies,8,9⇓ might prove …