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Amyloidogenic α-synuclein seeds do not invariably induce rapid, widespread pathology in mice

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An Erratum to this article was published on 09 October 2014

Abstract

In order to further evaluate the parameters whereby intracerebral administration of recombinant α-synuclein (αS) induces pathological phenotypes in mice, we conducted a series of studies where αS fibrils were injected into the brains of M83 (A53T) and M47 (E46K) αS transgenic (Tg) mice, and non-transgenic (nTg) mice. Using multiple markers to assess αS inclusion formation, we find that injected fibrillar human αS induced widespread cerebral αS inclusion formation in the M83 Tg mice, but in both nTg and M47 Tg mice, induced αS inclusion pathology is largely restricted to the site of injection. Furthermore, mouse αS fibrils injected into nTg mice brains also resulted in inclusion pathology restricted to the site of injection with no evidence for spread. We find no compelling evidence for extensive spread of αS pathology within white matter tracts, and we attribute previous reports of white matter tract spreading to cross-reactivity of the αS pSer129/81A antibody with phosphorylated neurofilament subunit L. These studies suggest that, with the exception of the M83 Tg mice which appear to be uniquely susceptible to induction of inclusion pathology by exogenous forms of αS, there are significant barriers in mice to widespread induction of αS pathology following intracerebral administration of amyloidogenic αS.

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Acknowledgments

This work was supported by the Ellison Medical Foundation Senior Scholar Award to TEG, the Wilder Family Fellowship to ANS, and funding from the University of Florida. We thank the University of Florida NeuroMedicine Human Tissue Brain Bank, which is supported by a gift from Eve and Joe Wilder, for the patient brain tissues. JR holds a Tier 2 Canada Research Chair and is funded by the Canadian Institutes of Health Research.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease and McKnight Brain Institute, College of Medicine University of Florida, Gainesville, FL, 32610, USA

    Amanda N. Sacino, Mieu Brooks, Michael A. Thomas, Alex B. McKinney, Nicholas H. McGarvey, Nicola J. Rutherford, Carolina Ceballos-Diaz, Todd E. Golde & Benoit I. Giasson

  2. Department of Laboratory Medicine and Pathobiology, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, M5S 3H2, Canada

    Janice Robertson

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  1. Amanda N. Sacino
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  2. Mieu Brooks
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  3. Michael A. Thomas
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  7. Carolina Ceballos-Diaz
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  9. Todd E. Golde
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  10. Benoit I. Giasson
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Correspondence to Todd E. Golde or Benoit I. Giasson.

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Sacino, A.N., Brooks, M., Thomas, M.A. et al. Amyloidogenic α-synuclein seeds do not invariably induce rapid, widespread pathology in mice. Acta Neuropathol 127, 645–665 (2014). https://doi.org/10.1007/s00401-014-1268-0

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  • DOI: https://doi.org/10.1007/s00401-014-1268-0

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