Neuroimaging outcomes in clinical trials in Alzheimer's disease.

The first disease modifying drugs targeting beta amyloid that were tested in phase II and III clinical trials have been disappointing. We believe that failures descended from a leaky drug development pipeline where insufficient attention has been devoted to valid animal models and valid imaging markers of disease progression. In the future, valid animal models will need to take into greater consideration the natural and molecular history of AD, where both beta amyloid and tau play a key role. Valid imaging markers of disease progression will need to be identified in humans and translated into animal versions. Future testing of putative disease modifying drugs in valid animal models with valid imaging markers of disease progression will allow to maximize the predictability of their effect in phase II and III clinical trials.