Fig. 10.

Cognitive impairment of hTau40^AT mice at 16 months of age. Morris water maze (MWM) test of 10 and 16 months old hTau40^AT mice in comparison to age-matched WT littermates. a, b At 10 months of age, spatial learning of hTau40^AT mice during a MWM acquisition is similar to WT controls and (b) hTau40^AT mice show a high preference for the target quadrant (>40 %), which is comparable to controls throughout all probe trials, indicating preservation of cognitive functions at 10 months of age. c In contrast, 16 months old hTau40^AT mice are impaired in learning the position of the hidden platform as demonstrated by significantly increased escape latencies during MWM acquisition in comparison to control mice (interaction effect, genotype x day, p = 0.033, F_(4,116) = 2.72). d Moreover hTau40^AT mice exhibit a lower preference for the target quadrant than WT animals from probe trial 2 onwards, pointing towards severe short- and long-term memory deficits due to accumulation of hTau40^AT at advanced age. a, c Data show mean escape latency (s) ± SEM for 10 months old WT (n = 14) vs hTau40^AT mice (n = 18) and 16 months old WT (n = 11) vs hTau40^AT mice (n = 20). Statistics: two-way repeated measure analysis of variances with post hoc Fishers LSD multiple comparisons test. Asterisks indicate a significant effect of interaction (genotype x day) between hTau40^AT mice and control group, *:p < 0.05. b, d Bars represent mean time in target quadrant (%) ± SEM for 10 months old WT (n = 14) vs hTau40^AT mice (n = 18) and 16 months old WT (n = 11) vs hTau40^AT mice (n = 20). Statistics: two-tailed Students t-test between hTau40^AT mice and control group for each probe trial, *:p < 0.05, ***:p < 0.001; n: number of mice; WT: wild-type animals; mo: months of age