The amyloid hypothesis provides a basis for the development of new therapeutic 
strategies in Alzheimer's disease. Two large trials have recently been 
published. The first is a phase 2 study of passive immunotherapy with 
bapineuzumab, a humanized anti-Abeta monoclonal antibody directed against the 
N-terminus of Abeta. This trial showed no differences within dose cohorts on the 
primary efficacy analysis. Exploratory analyses showed potential treatment 
differences on cognitive and functional endpoints in study completers and 
apolipoprotein E epsilon4 noncarriers. A safety concern was the occurrence of 
reversible vasogenic edema. The second study is a phase 3 trial of tarenflurbil, 
a modulator of the activity of gamma-secretase. Tarenflurbil had no beneficial 
effect on the primary or secondary outcomes. The tarenflurbil group had a small 
increase in frequency of dizziness, anemia, and infections. Possible 
explanations for the negative results of these trials may be related to the 
study design or the choice of dosage. However, it may also be that these 
negative findings reflect our still incomplete understanding of, at least part 
of, the pathogenesis of Alzheimer's disease.