Delaying the onset of APP overexpression attenuates hyperactivity but not anxiety in the open field assay. An independent cohort of animals was tested by open field assay at a single time point following 6 mo of APP overexpression. A A fraction of APP/TTA mice in both juvenile and adult onset groups show extreme hyperactivity, traveling >500 m in 30 min (5/15 juvenile onset, 4/26 adult onset), but most cover distances closer to the average of the other genotypes. B While both adult- and juvenile-onset APP/TTA mice travel greater average distances than other genotypes (p < 0.0001), delaying the onset of transgene expression significantly diminished hyperactivity compared to juvenile onset (***p < 0.001). C Juvenile-onset APP/TTA mice travel a smaller fraction of their total path within the center of the open field arena than control mice (p < 0.001 vs. NTG and APP, p < 0.01 vs. TTA). This difference is not normalized by delaying the onset of transgene expression. The only genotype for which dox rearing significantly altered path in center was APP (*p < 0.05). D A separate cohort of NTG and APP/TTA mice was reared on dox until 6 wk of age and then tested in the open field 8 mo later. Data from the 8 mo adult-onset mice are plotted alongside 6 mo juvenile-onset mice taken from panel A to provide a comparison of open field activity in mice matched for amyloid load rather than duration of APP overexpression. Again, delaying transgene onset reduces the fraction of mice displaying extreme hyperactivity (2/37 adult onset, 5/15 juvenile onset). E Average distance traveled is significantly reduced by delaying transgene onset (***p < 0.001). While open field activity of juvenile-onset APP/TTA mice is significantly higher than their NTG siblings (p < 0.05), adult-onset APP/TTA mice are no different than age-matched NTG controls (p > 0.05). F Despite significant attenuation of locomotor hyperactivity, delaying APP overexpression does not alter anxiety measured as % path in the center of the open field arena.