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A simplified illustration of a cross-sectional view of a rodent brain - AD - Tau PFF injection sites

Tau Model Overview

For this Alzheimer's disease model, we perform stereotaxic inoculation of preformed fibrils (PFFs) into the hippocampus and overlying cerebral cortex of PS19 transgenic mice [B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J]. These transgenic mice overexpress human tau with P301S mutation. The injection site was originally reported by Iba et al., J. Neurosci., 33: 1024-1037, 2013; doi: 10.1523/JNEUROSCI.2642-12.2013).

Tau Model Generation

A general schema for tau PFF animal model generation is:

AD - Tau PPF model Process

We can also use human brain extracts/homogenates as a substitute for the recombinant fibrils in this model.

A stereotaxic frame with a connected monitor, likely used in neuroscience to guide injections into specific brain regions such as the striatum and cortex for Alzheimer's Disease research

For this specific mouse model, we use PS19 male mice at 8 weeks-of-age. We then perform stereotaxic injection of sonicated, recombinant human tau PFFs or brain extracts into the hippocampus and overlying cortex. 

We use digital stereotaxic devices with automated microinjectors for high accuracy & precision.

This animal model is highly reproducible with a nearly 100% success rate of tau PFF seeding.

Our Tau Mouse Model Validated Measures

  • Body weight
  • Clinical scores
  • Neurofilament Light measures in plasma & CSF
  • Immunohistochemistry & multiplex immunofluorescence
Two brain tissue sections stained to reveal tau protein, associated with Alzheimer's Disease (AD), highlighting differences in tau accumulation in the hippocampus (HC) and cortex (Ctx).

AT8 tau immunohistochemistry staining at 12 weeks following stereotaxic injection of recombinant tau preformed fibrils.

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

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FAQs

What are the advantages of the tau fibril seeding/spreading model?

There are several advantages over simply using transgenic mice, including:

  • No need for prolonged aging of mice to observe a high level of tau pathology
  • Well-defined spatiotemporal pattern of tau pathology
  • Relatively short study duration
  • Models the seeding & spreading of misfolded tau protein implicated in Alzheimer's disease and other tauopathies

What is a "preformed fibril" (PFF)?

Preformed fibrils (PFFs) are recombinant, monomeric proteins (e.g. α-synuclein or tau) are incubated under specific conditions to generate aggregated, misfolded fibrils. These fibrils are then sonicated to generate short fibrils that can be used for in vitro or in vivo studies.

How long does the Tau Fibril Spreading model take?

We typically inject transgenic mice at 8 weeks-of-age and then allow for spreading for 2-3 months.

Can Biospective inject tau fibrils in other brain locations?

Yes. We can inject into any brain location using stereotaxic surgery. In fact, we have performed injections into the Anterior Olfactory Nucleus (AON) to determine if we observe a similar spatial pattern of spread as we see in our α-synuclein PFF model.

Can Biospective inject materials (e.g. oligomers, human brain extracts) provided by the Sponsor for model generation?

Yes. Our team has experience injection different types of inoculates into the brain using stereotaxic procedures.

More Information

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