Immunohistochemistry and biochemistry data

In the singe trangenic APP[V717I] mice, hAPP (isoform 695 with london mutation) is expressed under control of the neuron specific mouse Thy-1 promotor. As of 10.5 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. In this APP[V717I] transgenic mice, we have also proven that we can reduce Abeta levels with Abeta directed compounds, for example with the administration of DAPT, a gamma-secretase inhibitor (figure 2).

Representative photo collection of anti-Abeta 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] mice.


Figure 2: Orally administrated DAPT reduces soluble and insoluble Aβ levels in cortex and CSF 3 hrs post-dosing in 4.5 month-old APP[V717I] mice

Data on inflammatory markers

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 10 months (figure 3).

GFAP (astrogliosis) and CD45 reactivity

Figure 3: GFAP (astrogliosis) and CD45 reactivity in APP[V717I] transgenic mice as of 10 months, meaning an increase in brain inflammation. Quantification data is available on request.

Data on cognition and long term potentiation

Alzheimer’s disease is known from its distinct memory loss. Therefore it’s very important to search for therapies that can prevent memory loss or restore memory function in patients. Long term potentiation (LTP), a reflection of dendritic spine density and synaptic plasticity, is gaining importance as a functional ex-vivo or even in-vivo read-out related to learning and memory.

APP[V717I] transgenic mice show a clear LTP deficit, already present in a pre-plaque stage (8 months of age). Experimental Alzheimer treatments can show us (partial) recovering of the LTP in the CA1 region of APP[V717I] mice (figure 4). This makes LTP measurements the perfect tool for efficacy testing. We offer the LTP read-out in our transgenic models in collaboration with E-Phy-Science.

This impaired synaptic plasticity is also corroborated by demonstrating a cognitive deficit in APP[V717I] mice by using the Morris Water Maze. These mice show a less precise spatial reference memory compared to their non-transgenic counterparts (figure 5).

Orally administrated DAPT

Figure 4: LTP measurements in CA1 region of ~8-month-old vehicle or compound treated APP-ld animals (n=5 per group) (left). Average recording high frequency stimulation of 10-45 min post high frequency stimulation (right), * p<0.05, ** p<0.01.

Quadrant analysis during the probe trial

Figure 5: Quadrant analysis during the probe trial, Morris Water Maze with 6 months old APP[V717I] and age-matched non transgenic control animals.


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 APP-London model can be obtained upon request. Hereto, and for all other inquiries please contact the CRO team: cro[@]