reMYND’s APPxTau.P301L model combines both the APP-London and Tau.P301L human transgenes in one model which allows for assessing efficacy of drug candidates in one model.
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. These animals exhibit first a cognitive deficit as measured by Morris Water Maze (Figure 1) and impaired Long Term Potentiation (LTP), followed by a motor deficit (Figure 2) allowing for a longitudinal follow-up.
Figure 1: Morris Water Maze performance during the probe test, Annulus Crossing Index (ACI) represents the number of swims over the platform site in the TQ adjusted for swims over corresponding sites in other quadrants (Left) and time spent in target quadrant (Right) (N = 22-23 animals per group). Animals were tested before the onset of the motor phenotype.
Figure 2: Hind limb clasping of APPxTau.P301L animals observed between 8.4 and 13.2 months of age as observed by using the tail suspension test.