APP/PS1 Amyloid-Beta Transgenic Mouse Model of Alzheimer's Disease

Biospective's APP/PS1 mouse model of Alzheimer’s disease develops progressive amyloid-beta pathology with a well-defined spatiotemporal pattern. This robust amyloid model demonstrates Aβ plaques, cerebral amyloid angiopathy (CAA), neurodegeneration, and neuroinflammation (including activated microglia & reactive astrocytes). Biospective offers this validated APP transgenic mouse as part of its preclinical CRO services, supporting efficacy testing and target engagement studies using translational endpoints.

While a range of APP transgenic mouse models of Alzheimer's disease with human amyloid-beta expression exist, they each have their respective strengths and weaknesses.  Our APP/PS1 transgenic mice are well-suited for preclinical studies to support drug development pipelines, including efficacy testing, mechanism-of-action studies, PK/PD, and target engagement. A comparison of the APP/PS1 model to the 5xFAD mouse model can be found in our Resource - 5xFAD Mice & APP/PS1 Mice - A Comparison of Amyloid-β Mice for Alzheimer's Drug Development.

In this model, we have rigorously validated pathologic changes in the brains of these mice, including Aβ-related pathology, activated microglia, reactive astrocytes, and the spatial relationships between plaques and the neuroinflammatory microenvironment. We are well resourced to handle large-scale studies to generate high-quality data for our global biotech and pharmaceutical partners.

Overview of the APP/PS1 Model of Alzheimer's Disease

An mouse model with APP and PS1 mutations that is well-suited for preclinical drug development.

At Biospective, we have validated the APP/PS1 (ARTE10) transgenic mouse model of Alzheimer's disease. These mice feature pathologic changes that mimic  of these key hallmarks of human disease, including:

• Amyloid-beta (Aβ) plaques: Plaques begin to form in the anterior cerebral cortex at ~3 months-of-age and then progress with a time-dependent increase in burden and spatial extent.

• Cerebrovascular amyloid: Aβ deposits in leptomeningeal vessels and deep arterioles.

• Robust neuroinflammation: Pronounced activation of microglia and reactive astrocytes in the "neighborhood" of the plaques.

• Predictable time course: The spatiotemporal progression of pathology is well understood and the readouts are reproducible.

These mice are readily available at Biospective at ages appropriate for preclinical therapeutic studies.

A Novel Model of Alzheimer's Disease — Biospective's Amyloid-β and Tau Co-Pathology Mouse

An innovative mouse model based on AAV-driven expression of human tau in APP/PS1 mice.

A current limitation of many models of Alzheimer's disease is that they do not fully capture the spectrum of pathology that defines the human disease. To overcome this obstacle, our team at Biospective has developed and characterized a "co-pathology" model that by combines transgenic (APP/PS1 mice) and AAV vector-based methodologies.

This co-pathology model features the Aβ pathology characteristic of the APP/PS1 mouse, as well as intracellular phosphorylated wild-type human tau. In addition, this mouse model develops marked neuroinflammation, neurodegeneration, and associated functional impairments, reflecting the complex pathological interactions relevant to human Alzheimer's disease.

Biospective's APP/PS1 Model Expertise and Services

Biospective is a global neuroscience CRO with extensive experience in Alzheimer's disease animal models.

Our team at Biospective has 15+ years of experience conducting studies in Alzheimer's disease models. As such, we have unique expertise in the best use of these mice in preclinical drug development. Some key advantages of partnering with Biospective for Alzheimer's disease model studies studies include:

• Extensive Experience & Model Characterization: We have extensively characterized the APP/PS1 model through numerous studies. Our track record underscores our unique expertise with this AD model.

• End-to-End Preclinical Services: Biospective provides integrated services from study design through execution and data analysis. Our capabilities include comprehensive in-life assessments (behavioral testing, motor function assays, etc.), neuroimaging (MRI, CT), bioanalysis (fluid biomarkers, IHC & multiplex immunofluorescence), and expert data interpretation. This one-stop approach ensures consistency and accelerates timelines.

• Translational Biomarkers & Readouts: We incorporate translational endpoints that bridge preclinical findings to clinical outcomes. Our immunoassay capabilities include quantitative measures of neurofilament light chain (NfL), inflammatory cytokines, AB40/42, phosphorylated tau, and GFAP in mouse CSF, plasma, and brain homogenates. We also have core strengths in preclinical imaging, including in vivo MRI, PET/CT, and SPECT/CT for structural, functional, metabolic, and molecular imaging biomarkers. These readouts enhance the translatability of study results to human trials.

• Global Collaboration & Flexibility: We are a global preclinical neuroscience CRO serving biotech and pharmaceutical clients internationally. Our scientists collaborate closely with sponsors to tailor studies to specific therapeutic mechanisms or targets. We can accommodate custom endpoints or novel treatment paradigms. We also offer flexibility in study design to meet your program’s needs. Importantly, we prioritize scientific rigor, reproducibility, and open communication throughout the partnership.

By leveraging our core strengths, we are able to efficiently generate pharma-grade data from this model for small proof-of-concept projects as well as large, later-stage preclinical development studies.