In the APP[V717I]xPS1 bigenic mice, hAPP (isoform 695 with london mutation) is expressend in combination with human PS1[A246E] transgene both under control of the neuron specific mouse Thy-1 promotor. As of 6 months of age, these mice develop amyloid plaques in the hippocampus, cortex and subiculum. The formation of these amyloid plaques has been characterized both biochemically and immunohistochemically. Figure 1 confirms the development of these plaques with age, using the proprietary anti-Abeta Nanobody® and Thioflavin S.
Figure 1: Representative photo collection of anti-Abeta (proprietary anti-Abeta Nanobody®, reMYND/Ablynx, Belgium) and Thioflavin S stained sections showing total plaque load at different ages in APP[V717I]xPS1 mice.
BMS showed, in collaboration with reMYND, dose-dependent effects of sub-chronic donepezil on brain Aβ and cognition in APP[V717I]xPS1 mice. This study showed a significant improvement in reference memory in APPxPS1 mice along with a dose-dependent reduction in brain Aβ (figure 2). These results suggest that donepezil may alleviate cognitive impairments in Alzheimer’s disease, in part, by reducing brain Aβ.
Figure 2: Donepezil treatment results in a significant and dose-dependent improvement in reference memory along with similar reductions in brain amyloid-β (Aβ) in APP[V717I]xPS1 transgenic mice.
Over the last years inflammatory markers gained more and more interest in the Alzheimer’s disease field. There is a strong correlation between the onset of the plaques formation and the increase in neuronal inflammation. This is shown by an increase in inflammatory markers like GFAP and CD45 in the subiculum and cortex, starting at an age of 6 months (figure 3).
Figure 3: GFAP (astrogliosis) and CD45 reactivity in APP[V717I]xPS1 transgenic mice as of 6 months, meaning an increase in brain inflammation. Quantification data is available on request.
Moechars et al 1999, Van Dorpe et al 2000, Dewachter et al 2000, Terwel et al 2008, Tanghe et al 2010, Easton et al 2013, Jacobsen et al 2014
A proprietary data package on the APPxPS1 model can be obtained upon request. Hereto, and for all other inquiries please contact the CRO team: cro[@]remynd.com