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

Acta Neuropathol. 2014 May;127(5):645-65. doi: 10.1007/s00401-014-1268-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloidosis / metabolism*
  • Amyloidosis / pathology*
  • Animals
  • Brain / metabolism*
  • Brain / pathology*
  • Cells, Cultured
  • Escherichia coli
  • Gene Transfer Techniques
  • Humans
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Fibers, Myelinated / pathology
  • Neural Pathways / metabolism
  • Neural Pathways / pathology
  • Neurofilament Proteins / genetics
  • Neurofilament Proteins / metabolism
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Recombinant Proteins / metabolism
  • Species Specificity
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*


  • Neurofilament Proteins
  • Recombinant Proteins
  • SNCA protein, human
  • Snca protein, mouse
  • alpha-Synuclein
  • neurofilament protein L