In vivo detection of amyloid plaques in the mouse brain using the near-infrared fluorescence probe THK-265

Nobuyuki Okamura, Masanori Mori, Shozo Furumoto, Takeo Yoshikawa, Ryuichi Harada, Satoshi Ito, Yosuke Fujikawa, Hiroyuki Arai, Kazuhiko Yanai, Yukitsuka Kudo

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

Noninvasive detection of amyloid-β (Aβ) deposits in the brain would be beneficial for an early and presymptomatic diagnosis of Alzheimer's disease (AD). We developed THK-265 as a candidate near-infrared fluorescence (NIRF) probe for the in vivo detection of amyloid deposits in the brain. The maximal emission wavelength of THK-265 was greater than 650nm and it showed high quantum yield and molar absorption coefficients. A fluorescence binding assay showed its high binding affinity to Aβ fibrils (Kd = 97 nM). THK-265 clearly stained amyloid plaques in AD neocortical brain sections and showed a moderate log p value (1.8). After intravenous administration of THK-265 in amyloid-β protein precursor (AβPP) transgenic mice, amyloid deposits in the brain were clearly labeled with THK-265. Furthermore, in vivo NIRF imaging demonstrated significantly higher fluorescence intensity in the brains of AβPP transgenic mice than in those of wild-type mice. As THK-265 showed profound hyperchromic effect upon binding to Aβ fibrils, good discrimination between AβPP transgenic and wild-type mice was demonstrated even early after THK-265 administration. Furthermore, the fluorescence intensity of THK-265 correlated with amyloid plaque burden in the brains of AβPP transgenic mice. These findings strongly support the usefulness of THK-265 as an NIRF imaging probe for the noninvasive measurement of brain amyloid load.

Original languageEnglish
Pages (from-to)37-48
Number of pages12
JournalJournal of Alzheimer's Disease
Volume23
Issue number1
DOIs
Publication statusPublished - 2011

Keywords

  • Alzheimer's disease
  • amyloid
  • amyloid-β protein
  • fluorescence
  • molecular imaging

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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