What are key differences between PFF and AAV injected Parkinson's mice models?

While both types of models share several common features, such as robust neuroinflammation and neurodegeneration, there are specific differences. Based on the particular target(s) and mechanism(s)-of-action of a therapeutic agent, one model may possess advantages over the other. PFF-injected animals demonstrate spreading of misfolded α-synuclein fibrils, which is thought to be a key pathologic process in neurodegenerative diseases, including Parkinson’s disease. The specific phenotype depends on the injection site (neuroanatomical pathways targeted) and disease duration. These animals can develop widespread pathology throughout the brain (including dopaminergic and non-dopaminergic neurons) with a well-defined spatiotemporal pattern in cortical and subcortical structures, thereby replicating multiple motor and non-motor aspects of human PD. AAV-injected animals develop a strong phenotype associated with unilateral dopaminergic deficits. Behaviorally, these mice are similar to 6-hydroxydopamine (6-OHDA) lesioned animals, with the advantage that the pathology is driven by α-synuclein, rather than by a chemical toxin, thereby providing greater clinical relevance. These mice show selective degeneration of dopaminergic neurons in the substantia nigra pars compacta and concomitant loss of dopaminergic terminals in the striatum. Highly significant motor deficits can be readily measured in these mice (e.g. rotarod test) within a relatively short timeframe (2-3 months). Unilateral stereotaxic injection of AAV A53T α-synuclein vectors induces progressive loss of dopaminergic neurons in the substantia nigra pars compacta and associated motor and reflex deficits (e.g. swinging to the contralateral side). Note that pigmented neurons are shown only for illustrative purposes (mice do not have pigmented neurons in the substantia nigra

Parkinson's Disease Models

Q: What are the advantages of injecting PFFs into transgenic mice?

Transgenic mice overexpressing human α-synuclein have higher levels of α-synuclein expression in neurons compared to non-transgenic animals. As such, there is more “endogenous” α-synuclein “substrate” available for induced misfolding as part of the pathology spreading process. As a result, a greater level of α-synuclein aggregates can be observed in cell bodies and processes compared to that observed in wild-type mice. This greater burden of α-synuclein pathology leads to significant neuroinflammation (with activated microglia and reactive astrocytes) and neurodegeneration. As a consequence, distinct phenotypes with altered behavior, brain atrophy, changes in fluid biomarkers, etc., which can serve as robust readouts in preclinical efficacy studies, can be observed in these PFF-injected transgenic animals.

Q: How can neurodegeneration be measured in α-synuclein animal models?

In PFF-induced models, which show extensive neurodegeneration in multiple brain regions, in-life measures, such as MRI-based brain atrophy and blood & CSF neurofilament light chain, can be used. An advantage of these measures is that they can serve as clinically translation biomarkers. Read more about these measures in Brain Atrophy Analysis in Mouse Models of Neurodegeneration and Neurofilament Light Chain in Parkinson's Disease Models. In AAV-induced models, which demonstrate neurodegeneration of dopaminergic neurons localized to the substantia nigra and striatum, quantification of dopaminergic neuron nuclei, cell bodies, cell processes (axons, dendrites), and synaptic terminals can be readily achieved via immunohistochemistry or multiplex immunofluorescence. Examples can be seen in AAV A53T α-Synuclein Mouse Model of Parkinson's Disease and AAV α-Synuclein Models for Parkinson's Disease Drug Development.

Q: Can non-motor symptoms be observed in α-synuclein mouse models?

Non-motor symptoms are key features of human Parkinson’s disease. Depending on the injection site of the PFFs in transgenic α-synuclein-overexpressing mice, non-motor symptoms (e.g. sleep alterations, reduced olfaction, behavioral & cognitive deficits) can be found. For example, by targeting the limbic system, highly significant, progressive changes in sleep-wake cycles can be observed and quantitatively measured.

Models Overview

At Biospective, we develop and use rigorously characterized rodent models that closely reflect key features of human Parkinson's disease – including α-synuclein aggregation, dopaminergic neuron loss, neuroinflammation, motor impairments, and sleep disturbances. These models are designed to support investigations into disease mechanisms, pathological progression, and early-stage therapeutic effects with strong translational relevance.

Our animal model portfolio emphasizes reproducibility, well-defined phenotypes, and integration of behavioral, imaging, biochemical, molecular, and histopathological endpoints to enable comprehensive preclinical assessment. This scientific foundation allows researchers to explore pathogenic pathways, evaluate candidate therapeutic interventions, and generate robust data to inform drug development efforts.

α-Synuclein Preformed Fibrils (PFF) Models

The pathologic spread of misfolded alpha-synuclein that is characteristic of human Parkinson's disease can be modeled in animal brains by injection of α-synuclein preformed fibrils (PFFs). This "PFF seeding & spreading model" can be induced in transgenic mice overexpressing human α-synuclein or in wild-type mice or rats.

α-Synuclein PFF Model Induction

Injection of recombinant α-synuclein preformed fibrils (PFFs)
Applicable to
- M83 transgenic mice overexpressing A53T α-synuclein
- Wild-type mice or rats

α-Synuclein PFF Validated Injection Sites

Anterior Olfactory Nucleus (AON)
Medial Forebrain Bundle (MFB)
Striatum +/- Overlying Cerebral Cortex

α-Synuclein PFF Disease Features Modeled

Spreading of α-synuclein in a well-defined spatiotemporal pattern
Neuroinflammation
Neurodegeneration
Measurable behavioral impairments
- Motor deficits
- Non-motor symptoms (e.g. sleep disturbances)

These alpha-synuclein PFF PD models are highly reproducible for testing disease-modifying therapeutics.

At Biospective, we have over a decade of experience performing preclinical studies in α-synuclein PFF models of Parkinson's disease to evaluate:

Biodistribution
Target engagement
Mechanism-of-action
Therapeutic efficacy

MORE INFORMATION ON α-SYNUCLEIN PFF MODELS

3 validated injection sites of the Anterior Olfactory Nucleus (AON)

Our validated injection sites: Anterior Olfactory Nucelus (AON). Striatum +/- Overlying Cerebral Cortex, and Medial Forebrain Bundle (MFB).

IHC images showing phosphorylated α-synuclein of piriform cortex

Phosphorylated α-synuclein (pSyn129) IHC of ipsilateral (left) and contralateral (right) piriform cortex 12 weeks after unilateral α-synuclein PFF injection into the AON of an M83^+/- mouse.

Graphs showing elevated NF-L levels in plasma

Highly elevated levels of neurofilament light (NF-L) are observed in the plasma from the α-synuclein fibril seeding mice.

AAV-A53T α-Synuclein Models

Generation of α-synuclein pathology in the adult rodent brain can be generated via injection of adeno-associated virus (AAV) vectors. In this mouse model of Parkinson's disease, wild-type (C57BL/6) mice or genetically engineered models undergo stereotaxic injection by experts using digital stereotactic devices with automated microinjectors (for high accuracy and precision) of AAV vectors overexpressing A53T mutant human alpha-synuclein into the vicinity of the substantia nigra pars compacta.

AAV-A53T α-Synuclein Model Induction

Stereotaxic injection of adeno-associated virus (AAV) vectors overexpressing A53T mutant human α-synuclein

AAV-A53T α-Synuclein Validated Injection Sites

Substantia nigra pars compacta (SNc)

AAV-A53T α-Synuclein Disease Features Modeled

Dopaminergic neuron loss in the SNc & denervation of the ipsilateral striatum
Phosphorylated α-synuclein aggregates in the SNc & striatum
Neuroinflammation
Neurodegeneration
Unilateral motor deficits measurable through
- Rotarod test
- Tail suspension swing test (TSST)
- Cylinder test
- Hindlimb clasping test

At Biospective, we can also perform non-invasive imaging studies (e.g. MRI volumetry, [18F]FDG PET, [18F]DOPA PET) on these AAV-A53T α-synuclein models to generate clinically translational imaging biomarkers (e.g. regional brain atrophy, cerebral glucose hypometabolism, dopaminergic terminal loss).

The AAV-A53T α-synuclein Parkinson's disease model provides a robust and flexible system that is well-suited for studying the effects of therapeutic agents (e.g. small molecules, ASOs, gene therapies, biologics) on pathogenic mechanisms and functional impairments associated with Parkinson's disease.

MORE INFORMATION ON AAV-A53T α-SYNUCLEIN MODELS

Image showing dopaminergic neuron loss and denervation in caudate-putamen

Severe dopaminergic neuron loss and dopaminergic denervation in the ipsilateral (left hemisphere) caudate-putamen following unilateral AAV-hA53Tα-Syn injection into the SNc of a C57BL/6 mouse.

Graphs showing effects of loss of dopaminergic innervation on behavioral tests

Loss of dopaminergic innervation corresponds with unilateral motor deficits, including increased ipsilateral paw use (Cylinder Test), reduced latency to fall (Rotarod), and increased contralateral swings (Tail Suspension Swing Test).

Which Features of our Parkinson's Disease Models are Translatable to Human Disease?

Immunofluorescence of phosphorylated synuclein (pSyn129) in Parkinson's disease animal models reveals pronounced accumulation in neuronal soma and processes.

Alpha-Synuclein Aggregates

Aggregates of misfolded α-synuclein are a key pathologic feature of human Parkinson's disease. Lewy bodies and Lewy neurites are observed in dopaminergic neurons within the substantia nigra pars compacta, as well as in other brain regions. This misfolded α-synuclein pathology follows a characteristic spatiotemporal progression (Braak, 2003).

In our AAV- and PFF-induced Parkinson's disease animal models, we observe:

High levels of phosphorylated α-synuclein in neuronal soma and processes
Robust seeding and spreading of pathology in the PFF models

Activated microglia (red boxes) in the hippocampus of mice injected into the AON with PBS (top) or α-synuclein PFFs (bottom).

Activated Microglia & Reactive Astrocytes

Neuroinflammation is a key pathological feature of Parkinson's disease, with activated microglia and reactive astrocytes playing key roles in pathogenesis (Kam, 2020; Chen, 2023).

In our AAV- and PFF-induced Parkinson's mouse models, we observe:

Distinct spatiotemporal patterns of neuroinflammatory responses
Altered microglial and astrocytic morphology, detected using computer vision, machine learning, and deep learning algorithms developed in-house

See our Neuroinflammation Initiative: Microglia, Astrocytes, and Neurodegenerative Diseases

See our Innovation: Microglial Activation in an α-Synuclein Mouse Model of Parkinson's Disease

Graph showing AAV - EBST Test Results (Box and Whiskers)

Tail Suspension Swing Test showing that AAV-A53T α-syn mice exhibit increased contralateral swings due to a unilateral dopaminergic deficit, compared to AAV-null control mice.
**** p<0.0001.

Dopaminergic Neuron Loss & Motor Deficits

Extrapyramidal motor symptoms are a hallmark of Parkinson's disease, primarily driven by dopaminergic neuron loss in the substantia nigra pars compacta (SNc) and striatal denervation (e.g. caudate and putamen).

In our Parkinson's models, we induce pathology by targeting the SNc with either:

AAVs overexpressing α-synuclein, or
α-synuclein preformed fibrils (PFFs)

See our Resource: Preformed Fibrils – A Guide to Cell and Animal Models

These interventions result in:

Neurodegeneration of dopaminergic neurons in the SNc
Loss of dopaminergic terminals in the striatum
Motor impairments assessed by:

Graph showing M83 Sleep Bout Length % per bin

Sleep analysis showing that mice injected with α-syn PFFs into the AON exhibit disrupted sleep architecture, including shorter sleep bout lengths and reduced overall sleep duration.

Sleep Alterations

Sleep disturbances are among the most common non-motor symptoms of Parkinson's disease, affecting up to ~85% of patients (Stefani, 2020; Asadpoordezaki, 2025).

Using a non-invasive sleep monitoring system in Parkinson's disease mice, we have shown that:

α-synuclein PFF injection into the AON of A53T transgenic mice leads to:
- Altered sleep-wake architecture
- Changes in total sleep percentage
- Disrupted sleep bout lengths

MRI cortical thickness maps showing PBS-injected mice (top) and AON α-syn PFF-injected mice (bottom), with PFF-treated animals displaying cortical thinning.

Regional Brain Atrophy

Multi-modality brain imaging biomarkers are widely used in clinical trials of Parkinson's disease. MRI-derived measures of regional neuroanatomical volumes and cortical thickness are sensitive indicators of brain atrophy in Parkinson's disease (Tremblay, 2021; Abdelgawad, 2023).

Using whole-brain, high-resolution, anatomical MRI acquisition paired with advanced fully-automated image processing & analysis, we have shown:

Reproducible regional brain atrophy in both our AAV- and PFF-induced Parkinson's mice

See our Innovation: Brain Atrophy Analysis in Mouse Models of Neurodegeneration

α-Syn PFF-injected mice in the AON and MFB show elevated CSF NF-L levels compared to control mice.

Elevated Neurofilament Light in CSF & Plasma

Neurofilament light chain (NF-L) is elevated in the CSF and plasma of PD patients and is routinely used as a fluid biomarker in PD clinical trials (Bäckström, 2020; Urso, 2023; Pedersen, 2024). Increased NF-L levels have also been reported in several preclinical models of PD.

In our mouse models of Parkinson's disease, we observe:

Significant increases in plasma and CSF NF-L in M83^+/- transgenic mice following PFF injection of human α-synuclein into:
- The anterior olfactory nucleus (AON)
- The medial forebrain bundle (MFB)

See our Resource: Neurofilament Light Chain in Parkinson's Disease Models

What are the Pathological and Phenotypical Profiles of PFF and AAV α-Synuclein Rodent Models?

The tables below summarize the extent to which each model reproduces hallmark features of human Parkinson's disease, enabling rapid comparison of their relevance for specific research questions.

Pathology

This table outlines key PD-associated pathological features – such as α-synuclein aggregation, neuroinflammation, and dopaminergic neuron loss – and compares how robustly they emerge in PFF and AAV induced mouse models.

Feature/Domain	PFF Models	AAV Models
α-Syn Aggregates	✔️ Seeding & spreading	✔️
Neuroinflammation	✔️	✔️
Dopaminergic Neuron Loss	✔️ Moderate	✔️ Severe and selective DA cell loss in SNc & DA terminal loss in striatum

Functional Features

This table compares behavioral and physiological impairments linked to PD pathology, including motor deficits and sleep-wake disturbances, highlighting differences across mouse models.

Feature/Domain	PFF Models	AAV Models
Motor Deficits	✔️ Moderate motor phenotype; Measured in longer timeframe	✔️ Severe motor phenotype; Measured in shorter timeframe
Sleep Disturbances	✔️	N/A

Biomarkers

This table summarizes non-invasive imaging and fluid-based biomarkers relevant to disease progression. These biomarkers provide quantitative endpoints for assessing neurodegeneration and evaluating therapeutic effects across the PFF and AAV inducible animal models.

Feature/Domain	PFF Models	AAV Models
MRI Brain Atrophy	✔️	✔️
Neurofilament Light (NF-L)	✔️	✔️

Summary: Both PFF and AAV α-synuclein models exhibit pronounced α-synuclein pathology, with the PFF model showing characteristic seeding and spreading spatiotemporal patterns. Neuroinflammatory responses are observed in both models, whereas dopaminergic neuron loss is generally more severe and regionally selective in the AAV model. Motor impairments occur in both models, but arise earlier and with greater magnitude in the AAV model, and sleep-related phenotypes have not yet been evaluated in the AAV model. MRI-based brain atrophy and elevated NF-L serve as clinically translational biomarkers of neurodegeneration in both mouse models.

What are the Features of Parkinson's Disease Mouse Models?

The "Image Interactive" below allows you to explore our characterization of our AAV-A53T-Synuclein mouse model, including in vivo data and high-resolution images of entire Multiplex Immunofluorescence tissue sections.

You can simply navigate through the "Image Story" using the left panel.

You can pan around the high-resolution microscopy images using the left mouse button. You can zoom in and out using the mouse/trackpad (up/down) or the + and - buttons in the upper left corner. You can toggle (on/off), change color, and adjust image settings for the channels and segmentations in the Control Panel in the upper right corner.

We suggest using Full Screen Mode for the best interactive experience.

Neurodegeneration & Neuroinflammation in the AAV-Synuclein Mouse Model

1/12

This Interactive Presentation illustrates some of the interesting motor function, brain imaging, and pathologic features of Biospective's AAV A53T α-synuclein mouse model of Parkinson’s disease (PD).

This model was generated by injecting 12 week-old C57BL/6 mice with AAV-human-A53T-synuclein or AAV-null (control) vectors unilaterally into the left substantia nigra pars compacta (SNc). 2 µL of vector was infused at a rate of 0.4 µL/min using a digital stereotaxic device with an automated microinjector.

Coronal Image of Mouse Brain with AAV Injection Site in the SNc

Coronal Atlas View of SNc Injection Site

Multiplex immunofluorescence (mIF) images were generated by immunostaining for phospho-Syn129, GFAP, Iba-1, Tyrosine Hydroxylase, Dopaminergic Nuclei, and counterstained with the DAPI nuclear stain. Tissue sections were digitized using a high-throughput slide scanner and were processed using Biospective's PERMITS^TM software platform.

To navigate though this Image Story, you can use the arrows and/or the Table of Contents icon in the upper right corner of this panel.

You can also interact with the microscopy image in the viewer on the right at any time to further explore this high-resolution data.

Neurodegeneration in the Substantia Nigra

As can be seen in this microscopy image, there is substantial loss of TH-positive dopaminergic neurons in the ipsilateral SNc compared to the contralateral hemisphere. For reference, an illustration with atlas labels for this brain level is provided below.

Coronal Mouse Brain Section (Bregma -3.2) with Neuroanatomy Labels

Using our PERMITS^TM quantitative analysis software, we have quantified the TH staining in the SNc. The plots below show a highly significant reduction in the ipsilateral hemisphere.

Tyrosine Hydroxylase and Cell Density in the Substantia Nigra

TH stain density and cell density for AAV-Syn compared to AAV-null (control) injections; mean ± SEM, t-test, **** p<0.0001.

We have found significant brain atrophy in the SNc by generating regional volume data from in vivo anatomical MRI scans, which corresponds well with the loss of TH-positive neurons. MR images were acquired from mice injected with different doses of AAV-Synuclein at 4 weeks post-inoculation using a 7T animal MRI scanner.

Anatomical MRI with segmented SNc, as well as a plot of relative difference between ipsilateral and contralateral SNc. Injected AAV-Syn doses (GC) were 1×10⁹ (yellow), 5×10⁹ (blue), and 1×10¹⁰ (aqua). *p<0.05, **p<0.01.

Dopaminergic Neurons in the Contralateral SNc

This microscopy image shows the contralateral (right hemisphere) SNc which shows unaffected TH-positive cell bodies and processes in red. The DAPI-counterstained nuclei are shown in blue.

Loss of Dopaminergic Neurons in the Ipsilateral SNc

This microscopy image shows the ipsilateral (left hemisphere) SNc, which demonstrates a substantial reduction of TH-positive cell bodies and processes (in red) compared to the contralateral hemisphere. The DAPI-counterstained nuclei are shown in blue.

Neurodegeneration in the Caudate-Putamen & Dopaminergic Motor Deficits

This microscopy image show severe dopaminergic denervation of the ipsilateral (left hemisphere) caudate-putamen (loss of TH-positive terminals). For reference, an illustration with atlas labels for this approximate brain level is provided below.

Coronal Image of Mouse Brain at the Level of the Striatum

Coronal Mouse Brain Section (Bregma +0.86) with Neuroanatomy Labels

Using our PERMITS^TM quantitative analysis software, we have quantified the TH staining in the Caudate-Putamen. The plot below shows a highly significant reduction in the ipsilateral hemisphere.

Tyrosine Hydroxylase Staining in the Caudate-Putamen

TH stain density for AAV-Syn compared to AAV-null (control) injections; mean ± SEM, t-test, **** p<0.0001.

This loss of dopaminergic innervation corresponds well with unilateral motor deficits in these mice, including a highly significant increase in use of the ipsilateral paw during the Cylinder Test, decreased latency to fall in the Rotarod Test, and increased swings to the contralateral side in the Tail Suspension Swing Test (TSST).

Illustration of Motor Tests and Plots of AAV-Syn vs. AAV-null

Cylinder Test, Rotarod Test, and Tail Swing Suspension Test (TSST) data for AAV-Syn compared to AAV-null (control) injections; mean ± SEM, t-test, **** p<0.0001.

Loss of Dopaminergic Terminals in the Ipsilateral Caudate-Putamen

This high magnification view shows the severe extent of loss of dopaminergic (TH-positive) terminals in the ipsilateral striatum. There are some remaining (albeit dystrophic) axons present.

Similar to our findings in the SNc, we have observed brain atrophy in the caudate-putamen by quantitative analysis of high-resolution anatomical MRI scans, which establishes an in vivo-ex vivo relationship between neuroimaging and IF measures.

MRI Atlas and Volume Data at the Level of the Striatum

Anatomical MRI with segmented caudate-putamen, as well as a plot of the relative difference between ipsilateral and contralateral caudate-putamen. Injected AAV-Syn doses (GC) were 1×10⁹ (yellow), 5×10⁹ (blue), and 1×10¹⁰ (aqua). *p<0.05, **p<0.01.

Cerebrospinal Fluid (CSF) Neurofilament Light Chain (NF-L) in the AAV-Synuclein Mouse Model

NF-L is a neuron-specific cytoskeletal protein released into the extracellular fluid following axonal damage and/or neurodegeneration. Elevated NF-L levels serve as a highly sensitive biomarker for neuronal injury and damage.

In PD patients, NF-L concentrations are increased relative to healthy controls, and have been reported to correlate with clinical measures of disease severity and progression (Pilotto, 2021; Ou, 2024).

https://opt003stagmediafiles.blob.core.windows.net/image/1075128c3f6045a890167f0d44347615

CSF NF-L concentrations for AAV-Syn compared to AAV-null (control) injections; mean ± SEM, t-test, **** p<0.0001.

CSF NF-L quantification in the AAV-synuclein mouse model provides a sensitive and quantifiable readout of neurodegeneration.

Microgliosis in Response to Human A53T a-Synuclein Expression

In this low magnification image, one can readily appreciate the higher density of Iba-1 staining microglia in the ipsilateral hemisphere (indicated by the box) relative to the contralateral hemisphere in an AAV-Syn injected mouse brain.

The plots below show the Iba-1 stain density in various brain regions, with highly significant increased staining in the AAV-Syn mice.

Iba-1 stain density for AAV-Syn compared to AAV-null (control) injections; mean ± SEM, t-test, **** p<0.0001.

We have performed a morphological analysis of microglia using a novel computer vision & machine learning approach developed by our team. This fully-automated algorithm classifies non-activated (ramified) and activated (non-ramified) microglia.

Examples of Non-activated and Activated Microglial Morphology

The plots below show the microglial activation in various brain regions, with highly significant increased microglial activation in the AAV-Syn mice.

Plots of PERMITS Data Showing Activated Microglia

Microglial activation for AAV-Syn compared to AAV-null (control) injections; mean ± SEM, t-test, **** p<0.0001.

Iba-1 Staining in Proximity to Phosphorylated α-Synuclein

This high magnification view shows the increased density of Iba-1-stained microglia in areas with phosphorylated α-synuclein aggregates.

Astrogliosis in Response to Human A53T α-Synuclein Expression

This low magnification microscopy image show a higher density of GFAP-positive astrocytes in the ipsilateral hemisphere (indicated by the box) of an AAV-Syn injected mouse brain. The plots below show the GFAP stain density in various brain regions.

Plots of PERMITS Data Showing GFAP Stain Density

GFAP stain density for AAV-Syn compared to AAV-null (control) injections; mean ± SEM, t-test, **** p<0.0001.

Astrogliosis and Microgliosis

This high magnification microscopy image shows a high level of Iba-1-positive microglia and GFAP-positive astrocytes in the ipsilateral hemisphere. Note the “activated” morphology of these neuroinflammatory cells.

Summary

The AAV A53T α-syn mouse model recapitulates many of the hallmark features of Parkinson’s disease. This model demonstrates progressive development of asymmetric motor dysfunction (due to unilateral injection), and associated loss of TH-positive SNc neurons and striatal TH expression.

AAV A53T α-synuclein locally increases brain atrophy, microglial density and activation levels, and astrocyte density and hypertrophy. Studies are planned to further interrogate the spatial relationships between microglial activation, astrocyte hypertrophy, and α-synuclein aggregation.

The AAV A53T α-synuclein mouse model is well-suited for drug development given the quantitative in-life and ex vivo readouts. It also has advantages over other models as a screening tool for novel disease-modifying therapeutics targeting α-synuclein related pathology, including the relatively short timeframe required to perform preclinical studies in this model.

Please feel free to further explore the microscopy image in the viewer.

We would be happy to discuss this model and our characterization if you would like to Contact Us.

Table of Contents

Characterization of our AAV-A53T-Synuclein mouse model, including in vivo data and high-resolution images of entire Multiplex Immunofluorescence tissue sections.

Click to copy link

Parkinson's Disease Animal Models Summary: How do PFF and AAV α-Synuclein Models Compare?

Together, the PFF and AAV α-synuclein rodent models provide complementary platforms for investigating Parkinson's disease mechanisms and evaluating therapeutic strategies. Both reproduce core pathological features of the disease, including robust α-synuclein aggregation and measurable neuroinflammation, while differing in the expression and progression of key phenotypes. The PFF model offers a strong framework for studying seeding and spreading of pathology, whereas the AAV model demonstrates more pronounced and regionally selective dopaminergic neuron loss, along with earlier and more severe motor impairments. Although sleep-related phenotypes have not yet been assessed in the AAV context, both models support the use of MRI-based brain atrophy and NF-L levels in biofluids as translational biomarkers of neurodegeneration. Collectively, these models enable a comprehensive evaluation of Parkinson's disease-relevant pathways and therapeutic effects across diverse experimental objectives.

Learn more about our characterization of our Parkinson's Disease mouse models, our validated measures, and our Preclinical Neuroscience CRO services.

FAQs

What is α-synuclein?

α-Synuclein (alpha-synuclein) is a small, 140 amino acid presynaptic neuronal protein implicated in synaptic vesicle trafficking and neurotransmitter release. α-Synuclein can misfold and aggregate into oligomers and fibrils that deposit in Lewy bodies and Lewy neurites, the pathological hallmarks of Parkinson's disease and synucleinopathies. These aggregated forms of α-synuclein propagate in a stereotypical pattern across brain regions (). While the trigger for α-synuclein aggregation remains uncertain, factors such as neuroinflammation, mitochondrial dysfunction, and oxidative stress are believed to contribute to the process. See our Resource:

What are the key differences between the PFF and AAV models?

How well do these mice models translate to human Parkinson's disease?

What are the advantages of injecting PFFs into transgenic mice?

How can neurodegeneration be measured in α-synuclein animal models?

Can non-motor symptoms be observed in α-synuclein mouse models?

Can these models be used to test potential Parkinson's disease therapies?

References

Nordström, E., Eriksson, F., Sigvardson, J., Johannesson, M., Kasrayan, A., Jones-Kostalla, M., Appelkvist, P., Söderberg, L., Nygren, P., Blom, M., Rachalski, A., Nordenankar, K., Zachrisson, O., Amandius, E., Osswald, G., Moge, M., Ingelsson, M., Bergström, J., Lannfelt, L., Möller, C., Giorgetti, M., Fälting, J. ABBV-0805, a novel antibody selective for soluble aggregated α-synuclein, prolongs lifespan and prevents buildup of α-synuclein pathology in mouse models of Parkinson's disease. , : 105543, 2021;

Keywords

proteins are composed of linear chains of amino acids that must fold into a functional three-dimensional structure. When these chains fail to fold properly, the resulting proteins can adopt abnormal shapes. These proteins are typically insoluble, and disrupt normal cellular processes. The accumulation of misfolded proteins is closely linked with several neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic lateral sclerosis (ALS).

a neurodegenerative disease that is characterized by: (a) movement-related (motor) symptoms, including resting tremor, bradykinesia, rigidity, and postural instability, related to the loss of dopaminergic neurons in the substantia nigra; and (b) non-motor symptoms including anxiety, depression, apathy, hallucinations, constipation, orthostatic hypotension, sleep disorders, hyposmia/anosmia, and cognitive impairment.

Parkinson's Disease Mouse Models

Translational Parkinson's disease models, including α-synuclein preformed fibril (PFF) seeding & spreading models and AAV vector-induced α-synuclein models.

Models Overview

α-Synuclein Preformed Fibrils (PFF) Models

AAV-A53T α-Synuclein Models

Which Features of our Parkinson's Disease Models are Translatable to Human Disease?

Alpha-Synuclein Aggregates

Activated Microglia & Reactive Astrocytes

Dopaminergic Neuron Loss & Motor Deficits

Sleep Alterations

Regional Brain Atrophy

Elevated Neurofilament Light in CSF & Plasma

What are the Pathological and Phenotypical Profiles of PFF and AAV α-Synuclein Rodent Models?

What are the Features of Parkinson's Disease Mouse Models?

Parkinson's Disease Animal Models Summary: How do PFF and AAV α-Synuclein Models Compare?

Related Content

Up-to-date information on Parkinson's Disease and best practices related to the evaluation of therapeutic agents in PD animal models.

Preformed Fibrils - A Guide to Cell and Animal Models

Microglia, Astrocytes & α-Synuclein in Parkinson’s Disease

AAV α-Synuclein Models for Parkinson's Disease Drug Development

Neurofilament Light Chain in Parkinson's Disease Models

Microglial Activation in an α-Synuclein PFF Mouse Model

Mitophagy and Parkinson’s Disease

Autophagy, Parkinson's Disease, and Dopaminergic Neurons

Mitochondrial Dysfunction & Parkinson's Disease

More Information

Let us know what you’re interested in. Our team will be happy to discuss with you!