Longitudinal training improves MWM acquisition in the 3xTg-AD mice. Although all groups of experienced mice exhibited improved acquisition after repeated MWM training (A–D), this training effect was especially pronounced in 3xTg-AD mice. In particular, at 12 months of age, 3xTg-AD-h and 3xTg-AD-H mice were virtually indistinguishable from NonTg mice (A,C,D), whereas naive 3xTg-AD mice were severely impaired at every age after 6 months (C,D). However, at 15 months of age, 3xTg-AD mice were markedly impaired in MWM acquisition regardless of whether they had been previously trained or not. Specifically, at 15 months of age, homozygous 3xTg-AD mice showed significant acquisition deficits (D). However, a genotype effect was still present with hemizygous 3xTg-AD mice continuing to exhibit a training effect at 15 months of age (C). Each cluster of results represents the daily means across each group. Error bars indicate SE.