5xFAD (Familiar Alzheimer Disease) mice bear 5 mutations, 3 in the APP695 gene [APP K670N/M671L (Swedish), I716V (Florida), V717I (London)] as well as 2 mutations in the presenilin 1 gene [PS1 M146L, L286V] (Oakley et al., 2006). The expression of the 5xFAD transgene is driven by the neuron-specific Thy1 promoter.
5xFAD Transgenic Mouse Model (5xFAD Transgenic mice) highly overexpress Aβ1-40 and Aβ1-42 in the brain and cerebrospinal fluid which even increases over age. Histological analyses of the cortex and hippocampus revealed a dramatic plaque load and β-sheet formation accompanied by strong neuroinflammation. These pathological hallmarks also significantly increase over age. Animals present spatial and long term memory deficits as analyzed by the Morris water maze. Motor deficits were not detected.
5xFAD mice are thus a suitable model to study the influence of drugs on amyloid production, sequestration and deposition, the involvement of presenilin1 and inflammation.
Figure 1: Aβ42 level in the cortex (A) and hippocampus (B) of 3-, 6- and 9-month old 5xFAD mice. Immunoreactive (IR) area in percent; n = 3. Mean + SEM. One-way ANOVA with Bonferroni’s post hoc test. **p<0.01; ***p<0.001.
Figure 2: Quantification of neurofilament light chain in plasma and CSF of 5xFAD mice. A: NF-L levels in pg/ml in the plasma of 3, 6, 9 and 12 month old 5xFAD mice compared to non-transgenic littermates. Mean +SEM; n = 4-8. Two-way ANOVA with Bonferroni‘s post hoc test. B: Activated microglia in the cortex of 3, 6 and 9 month old 5xFAD mice. Immunoreactive area in percent in the cortex; n = 3. Mean + SEM. One Way ANOVA with Bonferroni’s post hoc test. *p<0.05; **p<0.01; ***p<0.001.