In this model, we perform stereotaxic inoculation of preformed fibrils (PFFs) into the hippocampus and overlying cerebral cortex of PS19 mice [B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J]. These transgenic mice overexpress human tau with P301S mutation. We have these mice in-licensed from University of Pennsylvania. The injection site was originally reported by the University of Pennsylvania group (Iba et al., J. Neurosci., 33: 1024-1037, 2013; doi: 10.1523/JNEUROSCI.2642-12.2013).
A general schema for PFF model generation is:
We can also use human brain extracts/homogenates as a substitute for the recombinant fibrils in this model.
For this specific 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 model is highly reproducible with a nearly 100% success rate of PFF seeding.
Our Validated Measures
- Body weight
- Clinical scores
- Neurofilament Light (NfL) measures in plasma & CSF
- Immunohistochemistry & multiplex immunofluorescence
Learn more about our characterization of this model and our validated measures.
Discover more of our Alzheimer's Models
What are the advantages of the 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)?
Recombinant, monomeric proteins (e.g. α-synuclein or tau) are incubated under specific conditions to generate aggregated, misfolded preformed 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 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.