Immunohistochemistry, biochemistry and behavioral data

In the combined model, expression of the human APP-london and Tau[P301L] transgenes is driven by the neuron-specific mouse Thy-1 promoter. The progressive Abeta pathology is observed in hippocampus, cortex and amygdala whereas the Tau pathology is observed in the brainstem, midbrain, cortex and at later age hippocampus (figure 1).

The Abeta and Tau pathology strongly correlates with the development of a motoric deficit. Figure 2 shows the increase of the clasping phenotype demonstrated by the tail suspension task in the bigenic APP[V717I]xTau[P301L] mice between an age of 8 to 13 months and a decrease in rotarod performance at 12 months of age.

Quantified Methoxy-X04 and AT100 (pTAU S212/T214)

Figure 1: Quantified Methoxy-X04 and AT100 (pTAU S212/T214) IHC staining of 6-13 months old APP[V717I] x Tau[P301L] animals in a specified area of the frontal cortex.

mice develop age-dependent motoric inabilities

Figure 2: APP[V717I]xTau[P301L] mice develop age-dependent motoric inabilities from ~10 months of age onwards

Data on cognition and long term potentiation

Memory loss is the most prominent clinical aspect of Alzheimer’s Disease. Ultimately, therapeutic interventions will only be valuable to patients if they can prevent memory loss or restore memory function.  Long term potentiation (LTP), a reflection of dendritic spine density and synaptic plasticity, is gaining importance as a functional ex-vivo or even in-vivo read-out related to learning and memory.

Chong and his coworkers observed a strong synaptic deficit, measured by LTP in the bigenic APP[V717I]xTau[P301L] model (biAT) in a pre-tangle stage (figure 3) and this measurement can serve as an excellent tool for efficacy testing of experimental Alzheimer treatments (Chong et al, 2011). We offer the LTP read-out in our transgenic models in collaboration with E-PHY-SCIENCE.

This impaired synaptic plasticity is also corroborated by demonstrating a cognitive deficit in the APP[V717I]xTau[P301L] mice by using the Morris Water Maze. These bigenic mice show a less precise spatial reference memory compared to their non-transgenic counterparts (figure 4).

LTP measurements in CA1 region of 4-6 months-old APP[V717I]xTau[P301L]

Figure 3: LTP measurements in CA1 region of 4-6 months-old APP[V717I]xTau[P301L] (biAT) animals compared to wild type animals and other transgenic Alzheimer models (Chong et all, 2011).

Quadrant analysis during the probe trial, Morris Water Maze with 9 months

Figure 4: Quadrant analysis during the probe trial, Morris Water Maze with 9 months- old APP[V717I]xTau[P301L] and age-matched non transgenic control animals (N = 22-23 per group, NE = Target Quadrant)

References

A proprietary data package on the APP[V717I]xTau[P301L] model can be obtained upon request. Hereto, and for all other inquiries please contact Bart Roucourt, CRO Manager.