Fig 1.
Transgenic hAPPLon/PS1A246E mice.
(A) Absolute body weight development; (B) Relative body weight development (% of day 0). *p<0.05 vs. individual experimental groups of hAPPLon/PS1A246E mice; (C) Plasma liraglutide concentrations determined on the same day after 1½ month of dosing (pre-dosing vs. 4h post-dosing). *p<0.05, **p<0.01 vs. pre-dosing, ##p<0.01 vs. liraglutide (100 ng/kg/day); (D) Survival rate of wild-type FVB/N x C57Bl/6J controls and hAPPLon/PS1A246E mice.
Fig 2.
Transgenic hAPPSwe/PS1ΔE9 mice.
(A) Absolute body weight development; (B) Relative body weight development (% of day 0). *p<0.05 vs. individual experimental groups of hAPPLon/PS1A246E mice; (C) Plasma liraglutide concentrations determined after 1, 3 and 5 months of daily dosing (pre-dosing vs. 3h post-dosing). *p<0.05, ***p<0.001 vs. pre-dosing; (D) Survival rate of C57Bl6 wild-type controls and hAPPSwe/PS1ΔE9 mice.
Fig 3.
Transgenic hAPPLon/PS1A246E mice.
Memory performance assessed in a Morris water maze task. Trial acquisition (training): (A) latency to platform, (B) % time spent in target quadrant, (C) swim speed. Spatial reference memory (probe trial): (D) latency to platform, (E) % time spent in target quadrant, (F) swim speed. **p<0.01, ***p<0.001 (wild-type FVB/N x C57Bl/6J controls vs. vehicle-dosed hAPPLon/PS1A246E mice).
Fig 4.
Transgenic hAPPSwe/PS1ΔE9 mice.
Memory performance assessed in a novel object recognition (A) and active-avoidance T-maze (B, C) task, respectively. (A) Novel object recognition index, (B) Number of trials in T-maze acquisition trial; (C) Number of trials in T-maze memory retention trial. *p<0.05 (vs. wild-type control), #p<0.05 (vs. baseline performance).
Fig 5.
Representative photomicrographs depicting β-amyloid plaque levels in eight month-old transgenic hAPPLon/PS1A246E mice.
(A-C) Plaque depositions in vehicle-dosed hAPPLon/PS1A246E mice, indicated at three individual coronal levels. (D) vehicle-dosed hAPPLon/PS1A246E mouse (E) liraglutide-treated hAPPLon/PS1A246E mouse (100 μg/kg/day); (F) liraglutide-treated hAPPLon/PS1A246E mouse (500 μg/kg/day).
Fig 6.
Representative photomicrographs depicting β-amyloid plaque levels in 12 month-old transgenic hAPPSwe/PS1ΔE9 mice.
(A-C) Plaque depositions in vehicle-dosed hAPPSwe/PS1ΔE9 mice, indicated at three individual coronal levels. (D) vehicle-dosed wild-type mouse, (E) vehicle-dosed hAPPSwe/PS1ΔE9 mouse, (F) liraglutide-treated hAPPSwe/PS1ΔE9 mouse (500 μg/kg/day).
Fig 7.
Stereological analysis of brain regional volume and plaque volume in transgenic hAPPLon/PS1A246E and hAPPSwe/PS1ΔE9 mice.
Stereological assessments were only performed in brain structures showing presence of β-amyloid plaques. Liraglutide treatment had no effect on brain regional volume and plaque load in hAPPLon/PS1A246E (A, B) and hAPPSwe/PS1ΔE9 (C, D) mice.
Table 1.
Total brain volume and plaque levels in two transgenic hAPP/PS1 mouse models of Alzheimer’s disease, as determined by stereological means.
Table 2.
Studies characterizing the effect of GLP-1 receptor agonists and other related compounds in different transgenic mouse models on β-amyloid plaque pathology.