Neurofibrillary tangle-like tau pathology induced by synthetic tau fibrils in primary neurons over-expressing mutant tau

FEBS Lett. 2013 Mar 18;587(6):717-23. doi: 10.1016/j.febslet.2013.01.051. Epub 2013 Feb 5.


Increasing evidence demonstrates the transmissibility of fibrillar species of tau protein, but this has never been directly tested in neurons, the cell type most affected by formation of tau inclusions in neurodegenerative tauopathies. Here we show that synthetic tau fibrils made from recombinant protein not only time-dependently recruit normal tau into neurofibrillary tangle-like insoluble aggregates in primary hippocampal neurons over-expressing human tau, but also induce neuritic tau pathology in non-transgenic neurons. This study provides highly compelling support for the protein-only hypothesis of pathological tau transmission in primary neurons and describes a useful neuronal model for studying the pathogenesis of tauopathies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Transmission, Infectious
  • Embryo, Mammalian
  • Escherichia coli / genetics
  • Gene Expression
  • Hippocampus / cytology*
  • Hippocampus / metabolism
  • Humans
  • Mice
  • Microscopy, Electron
  • Models, Biological
  • Mutation
  • Neurofibrillary Tangles / genetics
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / ultrastructure*
  • Primary Cell Culture
  • Protein Folding
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Tauopathies / genetics
  • Tauopathies / metabolism
  • Tauopathies / pathology
  • Transfection
  • tau Proteins / genetics*
  • tau Proteins / metabolism
  • tau Proteins / ultrastructure


  • Recombinant Proteins
  • tau Proteins