Candidate anti-Aβ fluorene compounds selected from analogs of amyloid imaging agents

Hyun Seok Hong, Izumi Maezawa, Madhu Budamagunta, Sandeep Rana, Aibin Shi, Robert Vassar, Ruiwu Liu, Kit S. Lam, R. Holland Cheng, Duy H. Hua, John C. Voss, Lee Way Jin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Alzheimer's disease (AD) is characterized by depositions of β-amyloid (Aβ) aggregates as amyloid in the brain. To facilitate diagnosis of AD by radioligand imaging, several highly specific small-molecule amyloid ligands have been developed. Because amyloid ligands display excellent pharmacokinetics properties and brain bioavailability, and because we have previously shown that some amyloid ligands bind the highly neurotoxic Aβ oligomers (AβO) with high affinities, they may also be valuable candidates for anti-Aβ therapies. Here we identified two fluorene compounds from libraries of amyloid ligands, initially based on their ability to block cell death secondary to intracellular AβO. We found that the lead fluorenes were able to reduce the amyloid burden including the levels of AβO in cultured neurons and in 5xFAD mice. To explain these in vitro and in vivo effects, we found that the lead fluorenes bind and destabilize AβO as shown by electron paramagnetic resonance spectroscopy studies, and block the harmful AβO-synapse interaction. These fluorenes and future derivatives, therefore, have a potential use in AD therapy and research.

Original languageEnglish (US)
Pages (from-to)1690-1699
Number of pages10
JournalNeurobiology of Aging
Issue number10
StatePublished - Oct 2010


  • Alzheimer's disease
  • Amyloid ligand
  • Amyloid-β
  • Electron paramagnetic resonance spectroscopy
  • Oligomer
  • Small molecules
  • Spin-label
  • Synapse

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Aging
  • General Neuroscience
  • Developmental Biology


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