Alzheimer’s Disease Mouse Models

Q: What are the key pathologic features found in the APP/PS1 transgenic mouse model?

In these transgenic mice, we find amyloid-beta (Aβ) plaque deposition beginning around 3 months-of-age, with a time-dependent increase in burden and extent. We see both fibrillar extracellular and intracellular beta-amyloid pathology, as well as parenchymal and vascular Aβ deposits. A key feature of this model is the strong level of neuroinflammation, with both astrogliosis and microgliosis (including activated microglia). You can learn more about the spatiotemporal relationships between Aβ plaques and neuroinflammatory cells in our Presentation - Amyloid-β & the Inflammatory Microenvironment in an APP/PS1 Mouse Model of Alzheimer's Disease.

Q: Are age-appropriate APP/PS1 mice readily available for studies?

Yes. We usually use 3 to 6 month-old APP/PS1 transgenic mice at the start of the dosing period. These mice are typically available to allow for rapid study initiation..

Q: What is the typical duration for studies using APP/PS1 mice?

These amyloid-β transgenic mouse models show an age-dependent progression of pathology. Depending on the mechanism-of-action & specific targets of the therapeutic intervention, as well as the specific readouts, we typically perform dosing for 3-6 months.

Q: Are activated microglia present in your Alzheimer's disease models?

Yes. Our β-amyloid and tau models show strong neuroinflammation (astrogliosis and microgliosis). These mice also show changes in microglia morphology which is consistent with that found in human Alzheimer's disease. You can read more about microglial morphology in neurodegenerative diseases in our Resource - Microglia Morphology in ALS, Alzheimer's Disease & Parkinson's Disease.

Amyloid-β Transgenic Models

The beta-amyloid pathology that is a hallmark of human Alzheimer's disease can be modelled via overexpression of mutant human amyloid precursor protein (APP) and presenilin 1 (PS1; PSEN1) in transgenic mice. Similar to human disease, the evolution of the pathology increases with age.

The APP/PS1 model that we use for preclinical evaluation of the efficacy of experimental, disease-modifying therapeutic agents is highly reproducible and replicates several key features of human AD. These mice show progressive development amyloid-beta (Aβ) plaques, cerebrovascular pathology, and neuroinflammation. The response to therapeutic intervention can be assessed by several quantitative readouts, including advanced image analysis of multiplex immunofluorescence staining of digitized brain tissue sections.

MORE INFORMATION ON AMYLOID-β MODELS

Tau Fibril Spreading Models

Generation of tau pathology in the adult mouse brain can be generated via inoculation of recombinant tau fibrils or human brain extracts. In this mouse model of Alzheimer's disease, P301S mutant tau (PS19) transgenic mice undergo stereotaxic injection of tau preformed fibrils (PFFs) into the brain to induce seeding & spreading of tau pathology.

This robust tau mouse model shows hyperphosphorylated tau aggregates in the cell bodies and processes of neurons, neuroinflammation (including activated microglia and reactive astrocytes), and neurodegeneration. Therapeutic efficacy can be evaluated using clinical assessments (e.g. change in body weight), measurement of neurofilament light chain (NfL; NF-L) in blood & CSF, and quantitative immunohistochemistry & multiplex immunofluorescence analysis.

More information on Tau Models

A microscopic view of brain tissue, specifically highlighting tau fibrils, which are associated with neurodegenerative diseases like Alzheimer's disease

Multiplex immunofluorescence is a primary readout for the evaluation of therapeutic efficacy in Alzheimer's disease mouse models. Quantitative measures, such as plaque load, phosphorylated tau density, activated microglia density, reactive astrocyte density, and neuronal loss, including the spatial relationships between misfolded protein pathology (e.g. amyloid-β plaques) and neuroinflammatory cells, can be derived from digitized tissue sections using computer vision & machine learning algorithms.

Learn more about our characterization of these Alzheimer's disease mouse models, our validated measures, and our Preclinical Neuroscience CRO services.

FAQs

What are the key pathologic features found in the APP/PS1 transgenic mouse model?

In these transgenic mice, we find beta-amyloid plaque deposition beginning around 3 months-of-age, with a time-dependent increase in burden and extent. We see both fibrillar extracellular and intracellular beta-amyloid pathology, as well as parenchymal and vascular Aβ deposits. A key feature of this model is the strong level of neuroinflammation, with both astrogliosis and microgliosis (including activated microglia). You can learn more about the spatiotemporal relationships between Aβ plaques and neuroinflammatory cells in our Presentation - .

Are age-appropriate APP/PS1 mice readily available for studies?

What is the typical duration for studies using APP/PS1 mice?

Are activated microglia present in your Alzheimer's disease models?

Alzheimer's Disease Mouse Models

Amyloid-β and tau mice with age-dependent disease progression, including neurodegeneration & neuroinflammation (activated microglia & reactive astrocytes).

Amyloid-β Transgenic Models

Tau Fibril Spreading Models

Related Content

Up-to-date information on Alzheimer's disease and best practices related to the evaluation of therapeutic agents in Alzheimer's disease animal models.

Amyloid-β & Inflammatory Microenvironment in Alzheimer's Mice

Microglia Morphology in ALS, Alzheimer’s Disease & Parkinson’s Disease

Amyloid-β Plaque Analysis in Alzheimer’s Disease

More Information

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