α-Synuclein Preformed Fibrils (PFF) Parkinson's Disease Models

The M83+/- transgenic (tg) mice demonstrate a significantly higher level of pathology in a shorter period of time compared to wild-type mice. They also demonstrate a range of progressive changes that can be measured during the in-life phase of the study, including elevated neurofilament light levels (NfL; NF-L) in the plasma & CSF, brain atrophy by in vivo MRI, and alterations in motor function, which we do not observe in the milder, wild-type (wt) mouse model.

Yes, we can do that. Our scientists would be happy to discuss the specifics of this type of animal model with you.

Yes. We maintain a well-established breeding colony of M83 transgenic synuclein mice so that mice are readily available for studies. Mice are typically aged to 8-12 weeks prior to inoculation with alpha-synuclein preformed fibrils (PFFs).

Preformed fibrils (PFFs) are recombinant, monomeric proteins (e.g. alpha-synuclein or tau) that are incubated under specific conditions to generate aggregated, misfolded fibrils. These fibrils are then sonicated to generate short fibrils that can be used for in vitro or in vivo studies.

Yes. That is a key advantage of this rodent model. We have a high level of alpha-synuclein pathology, microgliosis, astrogliosis, and neurodegeneration, so we can demonstrate a drug effect.

A good example can be found in the paper: Nordstrõm et al., ABBV-0805, an novel antibody selective for soluble aggregated α-synuclein, prolongs lifespan and prevents buildup of α-synuclein pathology in mouse models of Parkinson's disease. Neurobiol. Dis., 161: 105543, 2021; doi: 10.1016/j.nbd.2021.105543.

Yes. In particular, the MFB-injection Parkinson disease model demonstrates a number of motor deficits typically associated with loss of dopaminergic neurons in the substantia nigra. We have a wide range of motor function tests that are applicable to this mouse model.

We can do both. For analysis of spreading, the unilateral injection is ideal as it allows us to assess spread to the contralateral hemisphere. Bilateral injections can be advantageous when a higher level of pathology is desired or when we want equivalence between the brain hemispheres (for example, when one hemisphere will be used for IHC analysis and the other hemisphere for biochemistry or drug exposure analysis).

Yes. We see highly elevated levels of neurofilament light (NfL; NF-L) in the plasma and CSF of the alpha-synuclein fibril seeding mice.

We also observe highly significant brain atrophy of multiple regions, such as the piriform cortex and entorhinal cortex, via in vivo MRI (see Brain Atrophy Analysis in Rodent Models of Neurodegenerative Diseases).

We use a non-invasive, high-throughput system called PiezoSleep to measure sleep in these Parkinson disease mice (learn more about how we non-invasively measure sleep in mouse models). We find highly reproducible, progressive alterations of the sleep/wake cycles in this model. We commonly use this test to evaluate putative disease-modifying therapeutic agents in this mouse model.

Yes. In fact, we have specifically characterized activated microglia in these Parkinson's disease mice in our Presentation - Microglial Activation in an α-Synuclein Mouse Model of Parkinson's Disease.