Taconic and Transpharmation scientists demonstrate how to behaviorally and biochemically characterize the ARTE10 (APP-PS1) mouse model across three-time points relating to the early, middle, and late stages of amyloid progression.
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Increased startle response in ARTE10 compared to WT
Reduced PPI in ARTE10 compared to WT
Trending or increased signs of anxiety-like behavior and reduced risk-taking in ARTE10
Reduced nest building (scores range from 1-5) in ARTE10 compared to WT
Hypolocomotion in ARTE10 mice, could be due to increased anxiety-like behavior in a novel environment
No differences
ARTE10 mice are hyperactive on the running wheel
Supports the hypothesis that LMA hypoactivity may be anxiety-induced
Spatial working memory is impaired in cued learning and place learning in ARTE10 mice
Reversal learning is partially impaired in ARTE10 mice
To be completed: Reversal probe test, search strategies
| Indication | Test | ARTE10 Effect | Significance | |
|---|---|---|---|---|
| 5 months of age | 10 months of age | |||
| Anxiety | Canopy Test | ↑ | ↑↑ | ARTE10 – increased anxiety-like behavior |
| Motivation/Mood | Nest Building | ↓ | ↓ | Decreased motivation/mood (increased latency to nest and lower nest scores) |
| Sensory Motor gating | PPI | ↓ | ↓ | Deficits in sensory motor gating (reduced pre-pulse inhibition) |
| Activity | LMA | ↓ | ↓ | Hypolocomotion |
| Motor Function | Rotarod | NS | NS | No motor impairments |
| Activity | Running Wheel | ↑ | ↑ | Hyperactive |
| Learning | MWM | ↓ | ↓ | Spatial working memory deficit |
| Memory | MWM Y-Maze | NS NS | ↓ ↓ | Impaired working memory by 10 months |
MWM: Morris Water Maze, PPI: Pre-pulse inhibition, LMA: Locomotor Activity, NS: not significant
Plasma
CSF
Right hippocampus
Right cortex
BDNF levels in hippocampus and cortex were quantified using the MSD kit. Normality was assessed by the Shapiro-Wilk test. Data were considered parametric and were analyzed by unpaired t test. An alpha level of 0.05 was used as criterion for statistical significance. All data are presented as mean + SEM. * p<0.05
IFNγ, IL-1β, IL-6 and TNFα levels in plasma were quantified using the MSD kit. Normality was assessed by the Shapiro-Wilk test. IFNγ and IL-1β data were considered non-parametric and were analyzed by nonparametric Mann Whitney test. IL-6 and TNFα data were considered parametric and were analyzed by Welch’s t test. An alpha level of 0.05 was used as criterion for statistical significance. All data are presented as mean + SEM. Outliers were removed using ROUT (Q=5%). ** p<0.01
Nfl levels in plasma, CSF, hippocampus and Cortex were quantified using the MSD kit. Normality was assessed by the Shapiro-Wilk test. Plasma data were considered non-parametric and were analyzed by nonparametric Mann Whitney test. CSF, Hippocampus and Cortex data were considered parametric and were analyzed by unpaired t test with Welch’s Correction. An alpha level of 0.05 was used as criterion for statistical significance. All data are presented as mean + SEM. Outliers were removed using ROUT (Q=5%). **p<0.01
| Biomarker | Sample Type | Significance |
|---|---|---|
| NfL | Plasma | NS |
| CSF | Trending ↑ | |
| Hippocampus | NS | |
| Cortex | ↑ | |
| IFNY | Plasma | NS |
| IL-1B | Plasma | Trending ↑ |
| IL-6 | Plasma | NS |
| TNF-a | Plasma | ↑ |
| AB40 | Hippocampus | ↑ |
| Cortex | ↑ | |
| AB38 | Hippocampus | NS |
| Cortex | ↑ | |
| AB42 | Hippocampus | ↑ |
| Cortex | ↑ | |
| AB42/AB40 Ratio | Hippocampus | ↑ |
| Cortex | ↑ |
