Figure 6. Peripherally administered TAT-APPsweBBP improves hippocampal-dependent learning and memory in 5XFAD mice.

In order to correlate the BACE1 inhibitory activities of TAT-APPsweBBP with improved cognitive function, 5XFAD and WT control mice were randomized into three treatment groups: (1) TAT-APPsweBBP treated, (2) TAT peptide-treated and (3) PBS-injected mice (n = 10 per treatment, 5 female/5 male). The mice were treated with TAT-APPsweBBP, TAT-peptide (100 nmol/kg in 100 μL PBS) or PBS (100 μL) i.p. daily for 8 weeks. Following the treatment, hippocampal-dependent behavioral learning and memory was assessed with the radial arm water maze (RAWM, schedule as illustrated in (A). Cognitive ability was assessed as the number of entry-arm errors before finding the platform. (B) Compared to PBS or TAT-treatments, TAT-APPsweBBP enhanced cognitive ability, as evidenced by fewer errors. In contrast, there was no significant difference between WT treatment groups. (C, D) Sensorimotor ability was also assessed using the rotarod test in 5XFAD (C) and WT control (D) mice after treatment. TAT-APPsweBBP treatment tended to enhance motor activity in 5XFAD mice, as shown by increased latency to fall, but this did not reach a statistical level of significance when compared to either TAT peptide- or PBS-treated mice. All data are presented as mean ± SD (*P < 0.05, **P < 0.01, repeated measures 2-way ANOVA with LSD (B) or Bonferroni post hoc test (C and D).