Juvenile onset of transgenic APP leads to significant motor hyperactivity that can be attenuated by delaying transgene expression. A, B Locomotion was measured using an infrared photobeam system to track activity over time. Activity was identical in control (TTA single-transgenic) and APP transgenic mice (APP/TTA double-transgenic) immediately prior to (0 wk, A; n = 21 TTA, n = 33 APP/TTA) and one wk after the induction of transgenic APP expression in adult-onset mice (1 wk, B; n = 18 TTA, n = 19 APP/TTA). C, D Hyperactivity was apparent after 7 wk of transgenic APP expression (top row) in both juvenile- (**p < 0.01; n = 23 TTA, n = 20 APP/TTA) and adult-onset mice (**p < 0.01, n = 19 TTA, n = 20 APP/TTA). Both juvenile- (**p < 0.01, n = 12 TTA, n = 8 APP/TTA) and adult-onset mice (*p < 0.05, n = 11 TTA, n = 15 APP/TTA) remain hyperactive with continued transgene expression, although the degree of variability and the magnitude of difference between control and APP transgenic animals is greater with earlier onset (middle row). Suppression of transgene expression for 1 mo after 4 mo of overexpression normalized ambulation levels in APP transgenic mice to that of controls following adult (p = 0.85; n = 15 TTA, n = 14 APP/TTA) but not juvenile-onset (**p < 0.01; n = 15 TTA, n = 13 APP/TTA; bottom row). au: arbitrary units.