At what age do you start seeing β-amyloid plaques?

β-amyloid plaques are initially found in the frontal cortex at ~3 month-of-age.

What type of neuroinflammation do you see in this model?

We observe a very interesting spatiotemporal pattern of microgliosis (including activated microglia) and astrogliosis in this model. We have performed a detailed analysis, which can be found in our Presentation - Amyloid-β & the Inflammatory Microenvironment in an APP/PS1 Mouse Model of Alzheimer's Disease.

Do you see cerebral amyloid angiopathy (CAA) in this model?

We see extensive β-amyloid vascular pathology in this model. Amyloid staining can readily be observed in the leptomeningeal and deeper parenchymal blood vessels.

What areas of the brain show β-amyloid plaques in this mouse model?

Plaques are initially found in the frontal cortex and subiculum. As the mice age, there is a well-defined spatiotemporal pattern of β-amyloid pathology with extensive plaque burden in many brain regions, including the hippocampus and thalamus. We have performed a thorough characterization of this model from 3 to 15 months-of-age.

Amyloid-β Transgenic Mouse Models

Q: What promoter is used for transgene expression in the model?

The mutant human APP and PSEN1 transgenes are express under control of the Thy-1 promoter.

Amyloid Mouse Model Overview

β-amyloid pathology and cognitive impairment are hallmarks of sporadic and familial Alzheimer's disease. While multiple APP transgenic mouse models and APP knock-in mice models of Alzheimer's disease exist, which are typically based on overexpression of APP with one or more gene mutations, they each have their respective strengths and weaknesses.

At Biospective, we have validated the ARTE10 (APP/PS1) transgenic mouse model of Alzheimer's disease. Significant advantages of these transgenic mice include:

Amyloid-beta (Aβ) plaque deposition beginning around 3 months-of-age, with a time-dependent increase in burden and extent
Fibrillar extracellular and intracellular beta-amyloid pathology
Parenchymal and vascular Aβ deposits
Robust astrogliosis and microgliosis (including activated microglia)
Brain and spinal cord pathology

The mouse model time course is predictable and the measures are highly reproducible.

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

Amyloid Transgenic Model Generation

ARTE10 [C57BL/6NTac.CBA-Tg(Thy1-PSEN1*M146V,-APP*Swe)10Arte] (APP-PS1) homozygous mice are generated on a C57BL/6NTac background. ARTE10 is a transgenic (Tg) line with two co-integrated constructs: Thy-1 promoter specific expression the transgene coding for the 695 amino acid isoform that harbors the Swedish mutation of human amyloid precursor protein (APPsw), as well as human Presenilin 1 (PS1) carrying the M146V mutation (PS1M146V). This transgenic model expresses high concentrations of human amyloid-beta (Aβ) protein and aβ peptides via proteolytic processing (e.g. via β-secretases and γ-secretases), and develops human Alzheimer's disease-like amyloid pathology due to genetic mutations within the human amyloid precursor protein (APP) and PSEN1 genes. This Aβ generation (via amyloidogenic processing of APP) model has been used for non-invasive imaging of amyloid-β plaques using Amyloid PET imaging tracers.

Our Validated Amyloid Model Measures

Body weight
Neurofilament light chain in plasma & CSF
Immunohistochemistry & multiplex immunofluorescence
Spatial biology analysis (Read More in our Presentation - Amyloid-β & the Inflammatory Microenvironment in an APP/PS1 Mouse Model of Alzheimer's Disease)

Multiplex immunofluorescence staining (β-amyloid, Iba-1, GFAP) from a 9 month-old APP/PS1 mouse.

AD - Beta-amyloid Model - amyloid burden Graph

Time-dependent β-amyloid plaque formation in the frontal cortex.

Learn more about our characterization of this model, our validated measures, and our Preclinical Neuroscience CRO services.

Discover more of our Alzheimer's Models

Tau Fibril Spreading Models

FAQs

At what age are β-amyloid plaques initially seen?

What type of neuroinflammation is seen in the APP PS1 transgenic mouse model?

Is cerebral amyloid angiopathy (CAA) seen in the APP PS1 mice?

What promoter is used for transgene expression in the β-amyloid mice?

What areas of the brain show β-amyloid plaques in the β-amyloid transgenic mouse model?

Amyloid-β Transgenic Mouse Models

An APP/PS1 mouse model of Alzheimer's disease with progressive development of amyloid-beta (Aβ) plaques, vascular pathology, and neuroinflammation.

Amyloid Mouse Model Overview

Amyloid Transgenic Model Generation

Our Validated Amyloid Model Measures

Discover more of our Alzheimer's Models

Tau Fibril Spreading Models

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More Information

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