APPSL transgenic mice overexpress human APP751SL under the control of the murine Thy1 promoter. This human APP with London (717) and Swedish (670/671) mutations is expressed in high levels, resulting in an age-dependent increase of β-amyloid1-40 and -42. Starting at 3 – 6 months APPSL mice develop plaques consisting of amyloid depositions in the frontal cortex.
Cognitive deficits of these mice start at 9 to 10 month of age. Additionally, APPSL animals present with severe neuroinflammation and oxidative stress starting as early as 6 and 9 month of age, respectively. This model presents with an unchanged motor performance. Animals were already frequently used for efficacy studies.
Figure 1: Assessment of spatial learning in the Morris water maze showing distance traversed and escape latencies during 4 testing days of 6 (A, D), 9 (B, E) and 12 month (C, F) old APPSL (orange) and wild type WT (blue) animals. n = 13-21. Mean ± SEM. Two-way ANOVA with Bonferroni‘s post hoc test compared to WT. *p<0.05; **p<0.01; ***p<0.001.
Figure 2: Qualitative comparison of APPSL transgenic mice at 6, 9 and 12 month of age vs. a 12 month old non transgenic animal. Images show examples of immunofluorescent labeling of 6E10 (green) and collagen IV (red) on brain sections of a APPSL transgenic mouse at 6 (column 2 – B,F), 9 (column 3 – C,G) and 12 month (column 4 -D,H) of age compared to a 12 month old non transgenic animal (column 1 – A,E); nuclei are labeled with DAPI (blue).