Ruthenium red colorimetric and birefringent staining of amyloid-β aggregates in vitro and in Tg2576 mice

Nathan P. Cook, Clarissa M. Archer, Janelle N. Fawver, Hayley E. Schall, Jennifer Rodriguez-Rivera, Kelly T. Dineley, Angel A. Martí, Ian V.J. Murray

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Alzheimer's disease (AD) is a devastating neurodegenerative disease most notably characterized by the misfolding of amyloid-β (Aβ) into fibrils and its accumulation into plaques. In this Article, we utilize the affinity of Aβ fibrils to bind metal cations and subsequently imprint their chirality to bound molecules to develop novel imaging compounds for staining Aβ aggregates. Here, we investigate the cationic dye ruthenium red (ammoniated ruthenium oxychloride) that binds calcium-binding proteins, as a labeling agent for Aβ deposits. Ruthenium red stained amyloid plaques red under light microscopy, and exhibited birefringence under crossed polarizers when bound to Aβ plaques in brain tissue sections from the Tg2576 mouse model of AD. Staining of Aβ plaques was confirmed via staining of the same sections with the fluorescent amyloid binding dye Thioflavin S. In addition, it was confirmed that divalent cations such as calcium displace ruthenium red, consistent with a mechanism of binding by electrostatic interaction. We further characterized the interaction of ruthenium red with synthetic Aβ fibrils using independent biophysical techniques. Ruthenium red exhibited birefringence and induced circular dichroic bands at 540 nm upon binding to Aβ fibrils due to induced chirality. Thus, the chirality and cation binding properties of Aβ aggregates could be capitalized for the development of novel amyloid labeling methods, adding to the arsenal of AD imaging techniques and diagnostic tools.

Original languageEnglish (US)
Pages (from-to)379-384
Number of pages6
JournalACS chemical neuroscience
Issue number3
StatePublished - Mar 20 2013


  • Circular dichroism
  • Thioflavin S
  • amyloid β
  • birefringence
  • histochemistry
  • plaques
  • ruthenium red

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology


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