Together with these positive findings, it is important to note that the expression pattern of both APP and tau transgenes in the brain and retina of animal models of AD should not be misinterpreted as a precise reflection of the human disease. The layer and cellular burden of pathological Aβ and pTau aggregates is most likely governed by the promoter-driven expression of their corresponding transgenes. For instance, expression of the aggregate-prone mutant tau species in the P301S tauopathy mouse model is driven by the murine Thy1 promoter, which leads to the development of pathology in selected CNS cell types and consequently specific regions (Allen et al., 2002). In the retina, Thy1 is uniquely expressed by RGCs (Schmid et al., 1995) and therefore the intracellular aggregation of hyperphosphorylated tau in these cells and their nerve fibers is expected. This may underlie the common disparity in findings from stereological studies attempting to characterize regional and cellular susceptibility to AD pathology in CNS tissue from human versus animal models. Recent developments as well as ongoing efforts to fully characterize complete gene replacement animal models will be invaluable in addressing such limitations in several fields.