Distinct α-synuclein strains differentially promote tau inclusions in neurons

Cell. 2013 Jul 3;154(1):103-17. doi: 10.1016/j.cell.2013.05.057.


Many neurodegenerative diseases are characterized by the accumulation of insoluble protein aggregates, including neurofibrillary tangles comprised of tau in Alzheimer's disease and Lewy bodies composed of α-synuclein in Parkinson's disease. Moreover, different pathological proteins frequently codeposit in disease brains. To test whether aggregated α-synuclein can directly cross-seed tau fibrillization, we administered preformed α-synuclein fibrils assembled from recombinant protein to primary neurons and transgenic mice. Remarkably, we discovered two distinct strains of synthetic α-synuclein fibrils that demonstrated striking differences in the efficiency of cross-seeding tau aggregation, both in neuron cultures and in vivo. Proteinase K digestion revealed conformational differences between the two synthetic α-synuclein strains and also between sarkosyl-insoluble α-synuclein extracted from two subgroups of Parkinson's disease brains. We speculate that distinct strains of pathological α-synuclein likely exist in neurodegenerative disease brains and may underlie the tremendous heterogeneity of synucleinopathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / chemistry
  • Amyloid / metabolism
  • Animals
  • Cells, Cultured
  • Embryo, Mammalian / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Neurons / metabolism*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*
  • Recombinant Proteins / metabolism
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / metabolism*
  • tau Proteins / metabolism*


  • Amyloid
  • Recombinant Proteins
  • alpha-Synuclein
  • tau Proteins