Double transgenic combined Amyloid and Tau mouse model – APP[V717I]xTau[P301S] mouse model
Evaluate multi-target therapeutics in InnoSer’s combined APPxTau disease model
Characteristics of the combined APP[V717I]xTau[P301S] mouse model
The double transgenic APP[V717I]xTau[P301S] mouse model leverages two well-established transgenic mouse models of amyloid (APP[V717I] mouse model) and tau (Tau[P301S] mouse model) pathology. The double transgenic mice express human APP[V7I7I] with the London mutation and human Tau[P301S] (4R/2N) under control of the neuron-specific Thy-1 promoter, resulting in the combined and progressive development of β-amyloid and tau pathology within the same animal.
The APP[V717I]xTau[P301S] mouse model develops significant spatial learning and memory impairments in the Morris water maze from approximately 6.5 months of age, reflecting functional consequences of combined amyloid and Tau pathology. At later stages (around 9 months of age), the double transgenic mice also exhibit progressive motor deficits, including impaired rotarod performance and clasping behavior, indicative of advancing neurodegenerative processes.
Building on the robust amyloid phenotype of the APP[V717I] model and the aggressive Tau pathology of InnoSer’s Tau[P301S] model, the APPxTau[P301S] mouse provides a highly translational platform for comprehensive preclinical efficacy studies in Alzheimer’s disease.
✓ Double transgenic APPxTau show robust amyloid-β plaques and tau pathology across cortex, hippocampus and subiculum from an age of 8 months
✓ Amyloid-β plaques and tau pathology in the APP[V717I]xTau[P301S] mouse model is associated with robust neuroinflammation phenotype (astrocytosis, microgliosis) in cortex and subiculum at 9 months of age
✓ The double transgenic mice show cognitive impairment in Morris Water Maze paradigm from an age of 6.5 months
✓ APPxTau mice show progressive motoric impairment from an age of 9 months
Take advantage of InnoSer’s expertise, flexibility, and collaborative approach for your research. We support you in identifying new drug candidates, characterizing their pharmacological properties, and conducting rigorous safety and efficacy studies with state-of-the-art behavioral, bioanalytical, and histopathological readouts.
Example data featuring the APP[V717I]xTau[P301S] mouse model of Alzheimer’s disease
Progressive accumulation of plaque deposition (LOC), hyperphosphorylated Tau (AT100 = pThr212/pSer214 Tau), astrocytosis (GFAP) and microgliosis (CD45) in the cortex as measured by IHC
Data shown as mean ± SEM, n = 8, no data for WT at 11.2 months. Statistics: One-Way ANOVA, Tukey’s multiple comparison.
Preliminary data suggest Aβ accelerates the onset of and aggravates hTau pathology in APP[V717I]xTAU[P301S] transgenic mice
At 13 to 14 months of age hyperphosphorylation of Tau (AT8 staining) is significantly increased in APP[V717I] x Tau[P301S] transgenic mice compared to heterozygous Tau[P301S] mice, suggesting an interplay between APP / Ab and Tau. The onset of Tau hyperphosphorylation (at 8 months of age) seems accelerated as well.
The figure shows a quantification of AT8 (pTau S202/T205) positive neurons using IHC in the cortex. Similar patterns are detected in other brain regions with other pTau epitopes (AT100 in CA1 of the hippocampus and the cortex).
Your Alzheimer’s Disease Research Starts Here.
Explore our expertly curated comparison of available mouse models to make faster, data-driven decisions. View example study timeline, recommended readouts, and example data featuring validation datasets across the different mouse models.
Key readouts in the combined APP[V717I]xTau[P301S] mouse model
Original literature describing the combined Amyloid and Tau mouse model
- Terwel et al., 2008. Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice. DOI: 10.2353/ajpath.2008.070904
- Chong et al., 2011. Synaptic dysfunction in hippocampus of transgenic mouse models of Alzheimer’s disease: A Multi-electrode array study. DOI: 10.1016/j.nbd.2011.07.006
The People Behind Your Research
Sofie Carmans, PhD
Principal Scientist Neurology
Thomas Vogels, PhD
Principal Scientist Neurology
Frequently Asked Questions
Does the APPxTau[P301S] display both amyloid and tau pathology, and why is it relevant in terms of Alzheimer’s disease modelling?
Yes, InnoSer’s internal characterisation datasets show that the double transgenic APP[V717I]xTau[P301S] mouse model develops extracellular amyloid beta plaques (amyloid plaque load detected as LOC+ diffuse areas) and tau pathology (hyperphosphorylated tau detected by AT100+ regions) across the cortex and subiculum from 9 to 13 months of age, at which robust pathology is observed.
Importantly, our internal datasets show that Tau pathology in the combined model is moderately increased (see the dataset here) compared to the heterozygous Tau[P301S] model, suggesting that amyloid pathology aggravates Tau hyperphosphorylation and accelerates its progression.
Alzheimer’s disease is pathologically defined by the presence of both amyloid plaques and neurofibrillary tangles. While traditionally used transgenic Alzheimer’s disease mouse models, such as APP[V717I] or APPxPS1, display robust amyloid plaque deposition throughout the brain, they lack the associated plaque-driven tau pathology that is also central to the pathological development and progression of Alzheimer’s disease. Conversely, Tau[P301S] mice develop aggressive Tau pathology, but the P301S mutation in MAPT is linked to frontotemporal dementia (FTD), limiting the model’s standalone translational relevance for Alzheimer’s disease.
Because tau pathology remains largely absent in amyloid-only mouse models, incorporation of mutant human tau is required to recapitulate the dual hallmark pathology of Alzheimer’s disease in vivo.
Reach out to our scientific team to confirm this model’s suitability for your research.
Is the tau pathology observed in InnoSer’s double APPxTau transgenic mouse model driven by amyloid beta plaques?
InnoSer’s internal preliminary data suggest Aβ accelerates the onset of and aggravates tau pathology in the double transgenic APP[V717I]xTau[P301S] mice.
At 13 to 14 months of age, we observe significant increase in hyperhosphorylated tau (AT8 staining) in APP[V717I] x Tau[P301S] transgenic mice compared to heterozygous Tau[P301S] mice, suggesting an interplay between APP / Ab and Tau. The onset of Tau hyperphosphorylation (at 8 months of age) seems accelerated as well.
Quantification of AT8-positive neurons by immunohistochemistry in the cortex demonstrates this increase, with similar patterns observed in other brain regions and additional phospho-tau epitopes (e.g., AT100 in hippocampal CA1 and cortex).
These findings are consistent with literature suggesting that Aβ oligomers accelerate Tau pathology and cognitive impairment (Selkoe and Hardy, 2016; Spires-Jones and Hyman, 2014; Webster et al., 2014), supporting an amyloid-driven enhancement of Tau pathology.
What motor phenotypes are observed in the APP[V717I]xTau[P301S] model?
APP[V717I]xTau[P301S] mice develop progressive motor impairments starting around at 9 months of age, as evidenced by a clasping phenotype and impaired performance during the rotarod task. The clasping phenotype during the motor suspension test is commonly interpreted as a sign of neurodegenerative progression and corticospinal dysfunction.
These motor endpoints provide additional functional readouts of disease severity and can serve as sensitive measures of therapeutic efficacy at later stages.
Reach out to us to obtain the full mouse model phenotyping datasets.
Does the APP[V717I]xTau[P301S] model display cognitive deficits?
Yes, the combined model expressing mutant APP and Tau develops significant impairments in spatial learning and memory, including deficits in the Morris water maze from approximately 6.5 months of age.
The cognitive decline correlates with progressive accumulation of phosphorylated Tau and amyloid pathology, supporting the functional relevance of dual pathology.
However, as with all rodent models, mice do not recapitulate the full complexity of human cognition, social behavior, or clinical symptomatology. The model should therefore be interpreted as a mechanistic and translational efficacy platform rather than a complete replication of human Alzheimer’s disease.
Reach out to us to obtain the full mouse model phenotyping datasets.
Is InnoSer’s double transgenic APP[V717I]xTau[P301S] mouse model readily available for preclinical efficacy studies?
Yes, as an expert preclinical neurodegeneration CRO, InnoSer maintains access to established breeding cohorts of the double transgenic APP[V717I]xTau[P301S] mouse model, enabling rapid study initiation depending on the required animal age and genotype.
Our proactive colony planning ensures that your preclinical efficacy studies can be launched with minimal lead time.
InnoSer’s Available Alzheimer’s Disease Model Types
Amyloid (APP/ AB) Transgenic Mouse Models
InnoSer offers preclinical research services with several different transgenic amyloid models, which recapitulate the plaque pathology of AD.
Transgenic Tau Mouse Models
InnoSer offers unique research services with several different transgenic tau models, which recapitulate the Tau neurofibrillary tangle pathology of AD.
Tau Seeding & Spreading Mouse Models
InnoSer uses an AD brain extract injection model, providing unique preclinical services with a translational model of Tau pathology seeding and spreading.
In Vitro Neurology Assays
Screen your lead candidate compounds using InnoSer’s in vitro neurology assays to progress to preclinical in vivo studies with confidence
InnoSer’s Available Alzheimer’s Disease Mouse Models
Transgenic PS19 Mouse Model
Leverage one of the most widely used mouse models in preclinical research to evaluate the efficacy of your compound targeting tau pathology
![APP[V717I] mouse model](https://www.innoserlaboratories.com/wp-content/uploads/2026/05/APPV717I-mouse-model.png)
APP[V717I] mouse model
Tau[P301S] Mouse Model
Leverage InnoSer’s proprietary Tau[P301S] mouse model with reproducible and aggressive Tau pathology for fast, decision-driven preclinical efficacy studies
![APP[V717I] x PS1[A246E] mouse model](https://www.innoserlaboratories.com/wp-content/uploads/2026/05/APPV717I-x-PS1A246E-mouse-model.png)
APP[V717I] x PS1[A246E] mouse model
Test the efficacy of therapies targeting amyloid-beta accumulation, neuroinflammation, and cognitive impairment in an early-onset amyloidosis transgenic APPxPS1 Alzheimer’s disease model
![Tau[P301L] Mouse Model](https://www.innoserlaboratories.com/wp-content/uploads/2026/05/TauP301L-Mouse-Model.png)
Tau[P301L] Mouse Model
Leverage InnoSer’s Tau[P301L] mouse model with progressive, well-characterized Tau pathology for mechanism-driven preclinical efficacy studies
Transgenic APP x PS1 ARTE10 mouse model
Advance your amyloid-lowering therapeutic program by leveraging the widespread amyloid-beta pathology of the ARTE10 mouse model for robust preclinical efficacy studies
![APP[V717I] x Tau[P301S] mouse model, european neurology CRO specialists](https://www.innoserlaboratories.com/wp-content/uploads/2026/05/APPV717I-x-TauP301S-mouse-model.png)
APP[V717I] x Tau[P301S] mouse model
Evaluate multi-target therapeutics in InnoSer’s combined APPxTau disease model
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AAALAC Accreditation
InnoSer has earned the AAALAC accreditation, demonstrating our commitment to responsible animal care and use. AAALAC International is a nonprofit organization that promotes the humane treatment of animals in science through voluntary accreditation and assessment programs. InnoSer’s facilities in the Netherlands and Belgium have been AAALAC-accredited since 2016 and 2020, respectively. Read more about the AAALAC accreditation programme here.
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