BOX 1. TRANSLATIONAL CONCERNS WITH ANIMAL MODELS
† There is lack of concordance between preclinical models and human clinical trials.
– Potential reasons: wrong targets, incomplete models, lack of variability among individuals in
the models, patients enrolled too late, comorbidities
† Humans enrolled in clinical trials are heterogenous,whereas most models utilize in-bred stains on
mice.
– Potential solution: evaluating novel treatments in multiple lines may help address this point
† There is lack of substantial cell and synaptic loss in the majority of rodent models, suggesting the
models better represent the prodromal phase of the disease.
† Models are of familial AD, and most people have sporadic AD.