Methylene blue does not reverse existing neurofibrillary tangle pathology in the rTg4510 mouse model of tauopathy

Tara L Spires-Jones, Taylor Friedman, Rose Pitstick, Manuela Polydoro, Allyson Roe, George A Carlson, Bradley T Hyman

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease is characterized pathologically by aggregation of amyloid beta into senile plaques and aggregation of pathologically modified tau into neurofibrillary tangles. While changes in amyloid processing are strongly implicated in disease initiation, the recent failure of amyloid-based therapies has highlighted the importance of tau as a therapeutic target. "Tangle busting" compounds including methylene blue and analogous molecules are currently being evaluated as therapeutics in Alzheimer's disease. Previous studies indicated that methylene blue can reverse tau aggregation in vitro after 10 min, and subsequent studies suggested that high levels of drug reduce tau protein levels (assessed biochemically) in vivo. Here, we tested whether methylene blue could remove established neurofibrillary tangles in the rTg4510 model of tauopathy, which develops robust tangle pathology. We find that 6 weeks of methylene blue dosing in the water from 16 months to 17.5 months of age decreases soluble tau but does not remove sarkosyl insoluble tau, or histologically defined PHF1 or Gallyas positive tangle pathology. These data indicate that methylene blue treatment will likely not rapidly reverse existing tangle pathology.

Original languageEnglish
Pages (from-to)63-8
Number of pages6
JournalNeuroscience Letters
Volume562
DOIs
Publication statusPublished - 6 Mar 2014

Keywords

  • Amyloid beta-Peptides
  • Animals
  • Disease Models, Animal
  • Female
  • Male
  • Methylene Blue
  • Mice
  • Mice, 129 Strain
  • Mice, Transgenic
  • Neurofibrillary Tangles
  • Tauopathies
  • tau Proteins

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