MT1 + 2-deficiency reverts APP-associated inability to switch from a spatial to a stimulus–response strategy. Spatial memory and learning of 6-month-old females were assessed in the Morris Water Maze (MWM). a In the hidden platform phase, APP+ females showed impaired learning and memory as evidenced by the increased escape latencies. b APP+ females also showed impaired retention as evidenced by the decreased percentage of time spent in the target quadrant (TQ) during the probe trial tests. The dotted line in this graph represents the % of time, that by chance and not because of a learning process, mice can spend in the TQ. No differences due to MT1 + 2 deficiency were observed in any of these parameters. c When tested in the visible platform test, which in contrast to the hidden platform phase is best solved using a stimulus–response strategy rather than a spatial one, APPWT females showed higher escape latencies than the rest of the genotypes including APPMT1 + 2KO females. Data represents mean ± SEM (n = 6–9), and they were analyzed using either repeated measures using the GEE in a or day-by-day analysis using the generalized linear model (GLZ) in b: open diamond, p ≤ 0.04, filled diamond, p ≤ 0.05 versus APP− mice. In the visible platform test (c), genotype was used as a factor using the GLZ: plus, p ≤ 0.001 versus APPMT1 + 2KO mice