Development of novel amyloid imaging agents based upon thioflavin S

Jingjun Wei, Chunying Wu, David Lankin, Anil Gulrati, Tibor Valyi-Nagy, Elizabeth Cochran, Victor W. Pike, Alan Kozikowski, Yanming Wang

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

To date, small-molecule amyloid-imaging agents for in vivo detection and quantitation of amyloid deposits in Alzheimer's disease (AD) have been developed and successfully applied to human subjects. Preliminary studies have indicated that these amyloid-imaging agents were accumulated in the AD brains in a pattern that is relatively consistent with AD pathology, at least in the regions of amyloid-rich grey matter. These studies have also proven the concept that amyloid dyes, normally too hydrophilic to enter the brain, can be chemically modified to enhance brain permeability, binding affinity, as well as improve binding specificity for amyloid deposits. Related studies have suggested that structurally different agents can be developed that bind to different sites on amyloid deposits. In fact, in vivo cross-referencing studies based upon different amyloid-imaging agents may permit better characterization of AD pathology. But more importantly, novel amyloid imaging agents are required that will allow direct correlation between the results of animal models and human subjects based upon identical imaging modalities. Thus far, amyloid stains such as Congo red and thioflavin T have been extensively studied. However, another widely used amyloid dye, thioflavin S, has not been previously explored. This is in part due to the fact that thioflavin S exists as a mixture, not a pure chemical entity, albeit that the major component has been characterized. We hypothesized that neutral analogs, based upon the major component, could be developed as novel amyloid imaging agents, that exhibit complementary binding properties and pharmacokinetic profiles compatible with potential human studies.

Original languageEnglish (US)
Pages (from-to)109-114
Number of pages6
JournalCurrent Alzheimer Research
Volume2
Issue number2
DOIs
StatePublished - Apr 1 2005

Keywords

  • Alzheimer's disease
  • Amyloid
  • Congo red
  • Thioflavin S
  • Thioflavin T

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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