Imaging Aβ plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivative

William E. Klunk, Brian J. Bacskai, Chester A. Mathis, Stephen T. Kajdasz, Megan E. McLellan, Matthew P. Frosch, Manik L. Debnath, Daniel P. Holt, Yanming Wang, Bradley T. Hyman

Research output: Contribution to journalArticlepeer-review

Abstract

The identification of amyloid deposits in living Alzheimer disease (AD) patients is important for both early diagnosis and for monitoring the efficacy of newly developed anti-amyloid therapies. Methoxy-X04 is a derivative of Congo red and Chrysamine-G that contains no acid groups and is therefore smaller and much more lipophilic than Congo red or Chrysamine-G. Methoxy-X04 retains in vitro binding affinity for amyloid β (Aβ) fibrils (Ki = 26.8 nM) very similar to that of Chrysamine-G (Ki = 25.3 nM). Methoxy-X04 is fluorescent and stains plaques, tangles, and cerebrovascular amyloid in postmortem sections of AD brain with good specificity. Using multiphoton microscopy to obtain high-resolution (1 μm) fluorescent images from the brains of living PS1/APP mice, individual plaques could be distinguished within 30 to 60 min after a single i.v. injection of 5 to 10 mg/kg methoxy-X04. A single i.p. injection of 10 mg/kg methoxy-X04 also produced high contrast images of plaques and cerebrovascular amyloid in PS1/APP mouse brain. Complementary quantitative studies using tracer doses of carbon-11-labeled methoxy-X04 show that it enters rat brain in amounts that suggest it is a viable candidate as a positron emission tomography (PET) amyloid-imaging agent for in vivo human studies.

Original languageEnglish (US)
Pages (from-to)797-805
Number of pages9
JournalJournal of neuropathology and experimental neurology
Volume61
Issue number9
DOIs
StatePublished - Sep 2002
Externally publishedYes

Keywords

  • Alzheimer disease
  • Amyloid
  • Chrysamine-G
  • Imaging
  • Multiphoton microscopy
  • Positron emission tomography
  • Transgenic mice

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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