Tau Preformed Fibril (PFF) Seeding Mouse Model

Biospective’s tau PFF mouse model accelerates neurodegenerative disease drug development with translational tauopathy for preclinical research. As a global neuroscience CRO with expertise in tau PFFs injection into transgenic P301S (PS19) mice, we offer end-to-end in vivo services — including therapeutic efficacy, PK/PD, mechanism-of-action, and target engagement — supported by advanced imaging, quantitative IHC/IF, and clinically relevant biomarkers for biotech and pharma sponsors worldwide.

Overview of the Tau PFF Mouse Model

A disease-relevant tau mouse model for neurodegenerative disease preclinical drug development.

Biological Rationale and Disease Relevance

Tau aggregation and spread are key pathologic features of numerous neurodegenerative diseases, including frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Alzheimer's disease. In Biospective’s tau PFF mouse models, tauopathy is induced via the stereotaxic injection of recombinant human tau preformed fibrils into the brains of P301S tau transgenic mice (PS19 line). These fibrils seed endogenous tau misfolding and propagation through anatomically connected regions, recapitulating key features of human tauopathies, including neurofibrillary tangle-like pathology, neuroinflammation, and neurodegeneration.

All injections are performed by our expert team using digital stereotaxic devices with automated microinjectors for highly accurate and precise delivery of sonicated tau PFFs to the target region. A distinct advantage of our tau PFF model is acceleration of pathology compared to conventional transgenic models. We typically perform PFF injections into 8 week-old mice, thereby dramatically reducing study timelines.

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

Key Disease Features and Redouts of the Tau PFF Model

Biospective’s tau PFF mouse model faithfully recapitulates many hallmarks of tauopathy with clinically aligned endpoints for efficacy and target engagement studies.

Notable translational features observed in this model include:

• Misfolded tau aggregation and spread: Abundant phosphorylated tau inclusions (neurofibrillary tangle–like aggregates) develop and propagate in a stereotypical spatiotemporal pattern throughout connected brain regions. Pathology initiated at a focal injection site gradually appears in downstream regions (reflecting the prion-like spread of tau). The induction of pathology is highly penetrant (~100% of PFF-injected mice) and reproducible in its distribution.

• Robust Neuroinflammation: The model elicits activation of astrocytes and microglia in regions accumulating tau aggregates. This neuroinflammation (microgliosis, astrogliosis) parallels that seen in human brains, providing an opportunity to evaluate anti-inflammatory or immunomodulatory interventions. (See our Resource: Microglia, Astrocytes & Tau in Neurodegenerative Diseases)

• Neurodegeneration: Progressive loss of neurons and degeneration of their processes is a key outcome. This neurodegeneration is accompanied by surrogate biomarkers – for example, we observe elevated neurofilament light chain (NfL) levels in the plasma and CSF of tau PFF-seeded mice.

Accelerating Tau Therapeutic Testing

Biospective’s tau PFF mouse models is well-suited for efficacy testing, mechanism-of-action investigations, and target engagement evaluation of new tau-targeted disease-modifying therapies.

We have successfully employed this neurodegenerative disease model to test a wide range of therapeutic modalities, including small molecule neuroprotective compounds, antisense oligonucleotides (ASOs), gene therapies (e.g. AAV vectors), and antibody or vaccine-based immunotherapies. This model allows us to customize study endpoints to the specific mechanism of action of the therapy being tested. For example, we can assess target engagement by measuring reductions in tau pathology burden or changes in downstream signaling; we can evaluate biodistribution and pharmacodynamics by sampling tissues and fluids at various time points; and we can determine therapeutic efficacy by improvements in IHC/mIF and biomarker profiles relative to controls.

By partnering with Biospective, pharmaceutical and biotech researchers gain access to a thoroughly characterized, translationally relevant tau model and the scientific expertise to utilize it effectively to evaluate putative disease-modifying therapeutics. Biospective offers a unique combination of a well-established tau animal model and deep scientific know-how. Our tau PFF mouse model, coupled with our end-to-end preclinical CRO capabilities, positions us to be a valued preclinical partner in advancing novel tau-targeted therapies for neurodegenerative diseases.