Several second-generation active β-amyloid (Aβ) vaccines and passive Aβ 
immunotherapies are under clinical investigation with the aim of boosting Aβ 
clearance from the brain of the Alzheimer's disease (AD) patients. However, the 
preliminary cognitive efficacy of bapineuzumab, a humanized anti-Aβ monoclonal 
antibody, appears uncertain. Moreover, the occurrence of vasogenic edema and, 
more rarely, brain microhemorrhages, especially in apolipoprotein E ϵ4 carriers, 
have led to abandoning of the highest dose of the drug. Solanezumab, another 
humanized anti-Aβ monoclonal antibody, was shown to neutralize soluble Aβ 
oligomers, which is believed to be the more neurotoxic Aβ species. Phase II 
studies showed a good safety profile of solanezumab while studies on 
cerebrospinal and plasma biomarkers documented good signals of pharmacodynamic 
activity. However, the preliminary equivocal cognitive results obtained with 
bapineuzumab as well as the detrimental cognitive effects observed with 
semagacestat, a potent γ-secretase inhibitor, raise the possibility that 
targeting Aβ may not be clinically efficacious in AD. The results of four 
ongoing large Phase III trials on bapineuzumab and two Phase III trials on 
solanezumab will tell us if passive anti-Aβ immunization is able to alter the 
course of this devastating disease, and if Aβ is still a viable target for 
anti-AD drugs.