Figure 3

Delayed expression of transgenic APP reduces motor hyperactivity and normalizes body weight. A, B Comparison of mean ambulation recorded by infrared photobeam monitoring highlights the severity of hyperactivity observed in juvenile-onset APP transgenic animals (a) and the substantial reduction in this phenotype achieved by delaying onset until adulthood (b). Although reduced in magnitude with later onset, post-test analyses identified significant differences between genotypes for both adult- and juvenile-onset at 7 wk and 4 mo (**p < 0.01 for both at 7 wk; ***p < 0.001, for juvenile onset and *p < 0.05 for adult onset at 4 mo). C, D Replotting the data as individual values illustrates the wide range of locomotor activity seen in mice overexpressing APP from birth and the substantial decrease in both variance and average attained by delaying transgene onset. Individual mean ambulation is shown for juvenile vs. adult onset after 7 wk (C) and 4 mo (D) of transgenic APP expression. Post-test comparisons of groups matched for duration of expression magnifies the difference between genotypes for juvenile onset (***p < 0.001) but diminishes the difference for adult onset (p > 0.05 at both ages). E, F Mean body weight of APP-overexpressing mice is lower than controls at 7 wk (**p < 0.01) and 4 mo (*p < 0.05) in juvenile onset mice, and this difference persisted even after 1 mo of transgene suppression (*p < 0.05). Delaying transgene onset until adulthood normalized body weight of APP-overexpressing mice at all ages tested.