Whatever its mechanism of action, studies in transgenic mice were sufficiently compelling that Aβ immunization was taken into clinical trials in humans. In the first of these studies, the AN1792 trial, subjects were injected with an aggregated Aβ preparation similar to that used in the initial mouse studies. Although phase 1 studies indicated adequate immunological responses and tolerability of the vaccine, phase 2 studies in patients with AD were halted because of the appearance of an autoimmune meningoencephalitis in some patients.102 Although these initial studies were ultimately disappointing, a retrospective analysis found that those patients with the highest anti-Aβ titers had significantly less cognitive decline than those with low titers,103 arguing that active immunization remains a viable strategy if autoimmune side effects can be overcome. Most human trials are, however, currently pursuing passive immunization strategies because of the greater control over antibody levels that can be achieved as well as concerns over the ability of older subjects to mount an effective immune response. The farthest advanced of these trails at the time of writing is the Elan/Wyeth trial of AAB-001
