Drugs targeted at amyloid deposits in the brain failed to produce cognitive improvement in two recent studies in The New England Journal of Medicine. In the first study, more than 2000 patients with mild-to-moderate Alzheimer’s disease (AD) were randomly assigned to two different trials of the humanized monoclonal antibody solanezumab or placebo. Solanezumab preferentially binds soluble forms of amyloid and in preclinical trials promoted its clearance from the brain. After 80 weeks, there was no difference in any measure of cognitive function or functional ability (N Engl J Med 2014;370:311-321). In the second study, bapineuzumab, a humanized anti-amyloid-beta monoclonal antibody, was tested in two double-blind, randomized, placebo-controlled phase 3 trials involving patients with mild-to-moderate AD, about half with the APOE allele and half without. There was no significant difference in the primary outcomes after 78 weeks in any measure of cognitive change in either group (N Engl J Med 2014; 370:322-333). An accompanying editorial suggests that these studies have provided valuable information but have brought into question the value of some biomarkers in AD. These studies also point out that “we lack clarity on the roles that different forms of amyloid play in the disease” (N Engl J Med 2014;370:377-378).