Unique pathological tau conformers from Alzheimer's brains transmit tau pathology in nontransgenic mice

J Exp Med. 2016 Nov 14;213(12):2635-2654. doi: 10.1084/jem.20160833. Epub 2016 Oct 17.


Filamentous tau aggregates are hallmark lesions in numerous neurodegenerative diseases, including Alzheimer's disease (AD). Cell culture and animal studies showed that tau fibrils can undergo cell-to-cell transmission and seed aggregation of soluble tau, but this phenomenon was only robustly demonstrated in models overexpressing tau. In this study, we found that intracerebral inoculation of tau fibrils purified from AD brains (AD-tau), but not synthetic tau fibrils, resulted in the formation of abundant tau inclusions in anatomically connected brain regions in nontransgenic mice. Recombinant human tau seeded by AD-tau revealed unique conformational features that are distinct from synthetic tau fibrils, which could underlie the differential potency in seeding physiological levels of tau to aggregate. Therefore, our study establishes a mouse model of sporadic tauopathies and points to important differences between tau fibrils that are generated artificially and authentic ones that develop in AD brains.

Publication types

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

MeSH terms

  • Aging / pathology
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Animals
  • Brain / metabolism*
  • Brain / pathology*
  • Heparin / pharmacology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurofibrillary Tangles / pathology
  • Neurofibrillary Tangles / ultrastructure
  • Neurons / metabolism
  • Neurons / pathology
  • Phosphorylation
  • Protein Aggregates
  • Protein Conformation
  • Protein Isoforms / metabolism
  • Tauopathies / metabolism*
  • Tauopathies / pathology*
  • Tissue Extracts
  • tau Proteins / chemistry
  • tau Proteins / metabolism*


  • Protein Aggregates
  • Protein Isoforms
  • Tissue Extracts
  • tau Proteins
  • Heparin