Alzheimer’s Disease – APP Transgenic Mice
Test putative Alzheimer’s disease therapeutics using APP transgenic mice with amyloid beta plaque deposition and the downstream pathological events
APP Transgenic Mice Key Characteristics
The histopathological hallmarks of Alzheimer’s disease (AD) are extracellular plaques composed of Amyloid Beta (Aβ) and intracellular inclusions of the protein Tau (neurofibrillary tangles). Cleavage of the amyloid precursor protein (APP) leads to the generation of amyloid beta (Aβ) protein fragments.
Mouse models of amyloid pathology, namely APP transgenic mice, (over)express the human APP with familial AD-related mutations. Accordingly, APP transgenic mice recapitulate the Aβ aggregation cascade by expressing higher levels of the toxic Aβ1-40 and Aβ1-42 peptides. The biological and associated behavioural deficits observed in amyloid models make them a highly valuable model of AD, suitable for preclinical efficacy studies.
InnoSer offers unique contract research services using several mouse models of Alzheimer’s disease, including a range of APP transgenic models. APP Transgenic models can be used to study downstream pathological events such as neuroinflammation. As all transgenic models present with amyloid plaques, inflammation and cognitive deficits in different timeframes; the choice of the model ultimately depends on experimental compound’s mechanism of action and your research goals. Therefore, we recommend discussing your study setup in close collaboration with our experts.
✓ APP/PS1 (ARTE10) mouse model.
✓ APPSWE (Tg2576) mouse model.
✓ APPSWE-Tau mouse model.
✓ Humanized APP (APP-SAA Targeted Replacement) mouse model.
Take advantage of InnoSer’s expertise, flexibility, and collaborative approach for your research. Our in-house neurology experts have long-standing experience with modeling AD in vivo and are happy to help guide your decision on choosing the best model fit for your current research goals.
InnoSer’s neurology expert team possesses relevant experience in working with multiple therapy types, including small molecules, peptides, enzymes, oligonucleotides, gene therapy (viral vectors, e.g., AAVs), and immunotherapies (antibody/vaccine immunotherapies).
Your Neurology Research Starts Here.
Choose the Right Model for Your Research with Confidence
APP Transgenic Mice Sample Data
Amyloid mouse models show an impaired cognitive performance during the CognitionWall™ Discrimination learning
This deficit is already apparent at 12 weeks of age, before the appearance of plaques (~26 weeks). At 16 weeks, this deficit in discrimination learning can be rescued by an acute dose of the BACE1 inhibitor LY2886721. Using the CognitionWall™, we developed a one-night automated test to efficiently identify discrimination learning impairments in mice, without time-consuming handling of mice. The CognitionWall™ is a wall with three entrances in front of a food dispenser. Mice are rewarded with a food reward when they choose to pass through one of the three entrances. The rate at which a mouse gains a relative preference for the rewarded entrance is used as a measure of discrimination learning.
BACE1 inhibitors lower Aβ levels in plasma and brain
The number and size of amyloid plaques and associated neuroinflammation can be quantified after immunohistochemical (IHC) staining of brain slices. Aβ levels can be quantified in the brain, cerebrospinal fluid, and blood using ultra-sensitive immunoassays.
ARTE10 mice show progressive Aβ plaques (X04) and astrogliosis
In ARTE10 mice, methoxy-X04-positive amyloid plaque deposition is detected at 6 months (6M) of age, which becomes more pronounced at 10 months of age (10M). This is associated with reactive astrocytes (GFAP) around the plaques.
ARTE10 mice show progressive Aβ plaque (X04) deposition
In ARTE10 mice, methoxy-X04-positive amyloid plaque deposition is detected at 6 months (6M) of age, which becomes more pronounced at 10 months of age (10M).
ARTE10 mice show progressive astrogliosis
In ARTE10 mice, methoxy-X04-positive amyloid plaque deposition is detected at 6 months (6M) of age, which becomes more pronounced at 10 months of age (10M). This is associated with reactive astrocytes (GFAP) around the plaques.
Reactive microglia around plaques in ARTE10 mice
Iba1 (general microglia marker), shows clusters of microglia in ARTE10 mice. CD11B (neuroinflammation-related microglia marker) shows increases signal around plaques. MHC-II (neuroinflammation-related microglia marker) shows increased signal around the plaques.
APP Transgenic Mice Readouts
Biological Readouts
Test the efficacy of your treatments with the following biological readouts:
- MSD: Plasma, CSF, and brain (e.g., Aβ, cytokines, NfL).
- (Digital) histopathology
- Immunohistochemistry (e.g., Aβ plaques, phosphorylated Tau, microglia & astrocyte activation)
- Immunofluorescence and FISH
The People Behind Your Research
Thomas Vogels, PhD, In Vivo Neurology Study Director
Leads an expert team of scientists with vast experience in our Neurology models to help you choose the right model and guide your optimal study design. We provide the solution to accelerating your drug development.
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