Both models are well-established Parkinson’s disease mouse models for α-synuclein aggregation and spreading studies, but they differ in disease mechanism, kinetics, and translational application. 

The M83 hemizygous mice (A53T transgenic mouse model) provide a permissive genetic background that accelerates αlpha-synuclein aggregation following PFF injection. This results in earlier inclusion formation, more widespread pathology, and a faster disease induction timeline. The model is therefore highly suitable for efficacy studies requiring rapid readouts, robust pathology, and reproducible cohorts, particularly in a preclinical neurology CRO setting. 

Wild-type C57BL/6J mice injected with PFFs, in contrast, rely entirely on endogenous mouse αlpha-synuclein. This results in slower disease progression and a pathology course that more closely reflects sporadic Parkinson’s disease, which represents the majority of human cases. These models are often preferred for mechanistic studies and translational target engagement assessments, where transgenic overexpression may confound interpretation. 

Reach out to our team to identify which configuration is appropriate for your compound’s mechanism and species-specificity. 

The AAV-α-synuclein model and the α-synuclein PFF seeding model represent two complementary but mechanistically distinct Parkinson’s disease mouse models. The AAV-α-synuclein model uses viral vector–mediated overexpression of human alpha-synuclein (typically under a synapsin promoter) in dopaminergic neurons of the substantia nigra. This induces progressive alpha-synuclein accumulation and dopaminergic neuron loss driven primarily by protein overexpression toxicity. 

In contrast, the PFF seeding model induces pathology through templated misfolding and propagation of endogenous α-synuclein, closely modelling prion-like spreading mechanisms observed in human Parkinson’s disease. 

In collaboration with an academic partner, InnoSer (previously remynd team), has characterised an AAV-α-synuclein overexpression model to support its use in preclinical Parkinson’s disease research. The model consists of stereotactic unilateral injection of an AAV2/7 vector encoding human wild-type α-synuclein under the Synapsin-1 promoter into the substantia nigra of wild-type C57BL/6J mice, with study endpoints typically ranging from 4 to 9 weeks post-injection depending on the experimental design. Together with academic collaborators, the data have demonstrated robust and reproducible α-synuclein pathology in this model across independent experiments. Quantification of pSer129-α-synuclein shows strong aggregation at the injection site, accompanied by significant ipsilateral loss of TH+ dopaminergic terminals, reflecting progressive nigrostriatal degeneration. 

Contact our preclinical neurology team to learn whether the is suitable for your research now.

The alpha-synuclein PFF seeding model does not consistently develop robust or overt motor deficits within standard study timeframes. This reflects the biological nature of the model, which primarily captures progressive alpha-synuclein aggregation, prion-like propagation, regional spread, and associated neuroinflammatory responses.  

Importantly, at AD/PD 2026, InnoSer together with academic collaborators presented data on an AAV + mPFF combined alpha-synuclein model, demonstrating that integration of AAV-driven alpha-synuclein expression with PFF seeding results in clear motor deficits alongside robust pathological progression, providing a more translational platform for functional efficacy assessment. 

Therefore, if motor function is a key endpoint for your programme, this combined approach may be more appropriate. 

Contact our neuroscience team to discuss which Parkinson’s disease mouse model best aligns with your therapeutic mechanism and desired functional endpoints.