Drs. Jacob Ayers, Ben Giasson, graduate student, Nicole Rutherford & colleages publish in Jan 2017 Journal of virology

Ayers JI, Brooks MM, Rutherford NJ, Howard JK, Sorrentino ZA, Riffe CJ, Giasson BI. Robust Central Nervous System Pathology in Transgenic Mice following Peripheral Injection of alpha-Synuclein Fibrils. J Virol 2017; 91(2).


Misfolded α-synuclein (αS) is hypothesized to spread throughout the CNS by neuronal connectivity leading to widespread pathology. Increasing evidence indicates that it also has the potential to invade the CNS via peripheral nerves in a prion-like manner. Based on the effectiveness following peripheral routes of prion administration, we extend our previous studies of CNS neuroinvasion in M83 αS transgenic mice following hindlimb muscle (IM) injection of αS fibrils by comparing various peripheral sites of inoculations with different αS protein preparations. Following intravenous injection in the tail vein of M83+/+ mice, robust αS pathology was observed in the CNS without the development of motor impairments within the time frame examined. Intraperitoneal (IP) injections of αS fibrils in M83+/- mice resulted in CNS αS pathology associated with paralysis. Interestingly, injection with soluble, non-aggregated αS resulted in paralysis and pathology in only a subset of mice, whereas soluble Δ71-82 αS, human βS, and KLH control proteins induced no symptoms or pathology. IP injection of αS fibrils also induced CNS αS pathology in another αS transgenic mouse line (M20), albeit less robust in these mice. In comparison, IM injection of αS fibrils was more efficient in inducing CNS αS pathology in M83 mice than IP or tail vein injections. Furthermore, IM injection of soluble, non-aggregated αS in M83+/- mice also induced paralysis and CNS αS pathology, although less efficiently. These results further demonstrate the prion-like characteristics of αS and reveal its efficiency to invade the CNS via multiple routes of peripheral administration.


The misfolding and accumulation of α-synuclein (αS) inclusions is found in a number of neurodegenerative disorders and is a hallmark feature of Parkinson’s disease (PD) and PD-related diseases. Similar characteristics have been observed between the infectious prion protein and αS, including its ability to spread from the peripheral nervous system and along neuroanatomical tracts within the central nervous system. In this study, we extend our previous results and investigate the efficiency of intravenous (IV), intraperitoneal (IP), and intramuscular (IM) routes of injection of αS fibrils and other protein controls. Our data reveals that injection of αS fibrils via these peripheral routes in αS overexpressing mice are capable of inducing a robust αS pathology and in some cases cause paralysis. Furthermore, soluble, non-aggregated αS also induced αS pathology, albeit with much less efficiency. These findings further support and extend the idea of αS neuroinvation from peripheral exposures.