Immunohistochemistry, biochemistry and behavioral data

The interplay ofand Tau is still considered detrimental if not crucial for disease etiology and progression of Alzheimer’s Disease. You can now also assess the effects of your experimental Alzheimer’s Disease treatment on both amyloid- and tau pathology in the cross of our APP-london and Tau.P301S transgenic mouse models, in which APP-london aggravates the Tau-effect.

In the combined model expressing the human APP-london and human Tau.P301S heterozygous transgenes (under the control of neuron-specific Thy-1 promoter), progressive Tau pathology is observed in the cortex (Figure 1, Figure 2), hippocampus, midbrain and hindbrain (Figure 1). Compared to the single transgenic heterozygous Tau.P301S transgenic model, the double transgenic mouse shows enhanced Tau pathology suggesting the expression of APP-london mutant promotes formation of Tau aggregates.

APP-london mutation worsens Tau pathology in the double heterozygous transgenic

Figure 1: Introduction of the APP-london mutation worsens Tau pathology in the double heterozygous transgenic APP-london x Tau.P301S transgenic mouse model (in blue) compared to the single transgenic Tau.P301S mouse model (green). The evolution over time of counts of AT100 (pTau S212/T214) positive aggregates in the frontal cortex (left) and the cerebellar nuclei (IntP, IntA and LatPC) (right) is shown. Statistics: students T-test * p<0.05, ** p<0.01

APP-london mutation worsens Tau pathology in the double heterozygous transgenic

Figure 1: Introduction of the APP-london mutation worsens Tau pathology in the double heterozygous transgenic APP-london x Tau.P301S transgenic mouse model (in blue) compared to the single transgenic Tau.P301S mouse model (green). The evolution over time of counts of AT100 (pTau S212/T214) positive aggregates in the frontal cortex (left) and the cerebellar nuclei (IntP, IntA and LatPC) (right) is shown. Statistics: students T-test * p<0.05, ** p<0.01

These animals exhibit a cognitive deficit at 6.5 months of age (before the onset of a motor deficit) in the Morris water maze task (spatial reference memory) followed by a motor deficit starting at 8 months allowing for a longitudinal follow-up (Figure 3). Compared to the single transgenic heterozygous Tau.P301S transgenic model, introduction of the APP-london mutation seems to worsen the memory and motoric deficit. This trend is confirmed in the respective learning curves of the Morris Water Maze task (data not shown).

P301S transgenic mouse model shows a cognitive deficit

Figure 3: The double transgenic APP-london x Tau.P301S transgenic mouse model shows a cognitive deficit at 6.5 months in a Morris water maze task (left) and a progressive motoric deficit (tail suspension task) starting from 8 months onwards (right). The single transgenic heterozygous Tau.P301S model is shown in green whereas the APP-london x Tau.P301S transgenic mouse model is shown in blue. Statistics: One-Way ANOVA Tukey’s multiple comparison, * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001

A proprietary data package on the APP[V717I]xTau[P301S] model can be obtained upon request. Hereto, and for all other inquiries please contact Bart Roucourt, CRO Manager.