title: Use of a benzimidazole derivative BF-188 in fluorescence multispectral imaging for selective visualization of tau protein fibrils in the Alzheimer's disease brain.
abstract: OBJECTIVE
  Selective visualization of amyloid-β and tau protein deposits will help to understand the pathophysiology of Alzheimer's disease (AD). Here, we introduce a novel fluorescent probe that can distinguish between these two deposits by multispectral fluorescence imaging technique.
  
  
  METHODS
  Fluorescence spectral analysis was performed using AD brain sections stained with novel fluorescence compounds. Competitive binding assay using [(3)H]-PiB was performed to evaluate the binding affinity of BF-188 for synthetic amyloid-β (Aβ) and tau fibrils.
  
  
  RESULTS
  In AD brain sections, BF-188 clearly stained Aβ and tau protein deposits with different fluorescence spectra. In vitro binding assays indicated that BF-188 bound to both amyloid-β and tau fibrils with high affinity (K i  < 10 nM). In addition, BF-188 showed an excellent blood-brain barrier permeability in mice.
  
  
  CONCLUSIONS
  Multispectral imaging with BF-188 could potentially be used for selective in vivo imaging of tau deposits as well as amyloid-β in the brain.
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Harada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.forename: Shozo
authors.initials: S
authors.lastname: Furumoto
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
authors.forename: Yukitsuka
authors.initials: Y
authors.lastname: Kudo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D000682:Amyloid / Q000032:analysis / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002070:Butadienes / Q000737:chemistry; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D008297:Male; D051379:Mice; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010539:Permeability; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D013050:Spectrometry, Fluorescence; D016875:tau Proteins / Q000032:analysis* / Q000378:metabolism
chemical_list: C000591377:2-((4-(4-methylamino)phenyl)-1,3-butadienyl)benzimidazole; D000682:Amyloid; D016229:Amyloid beta-Peptides; D001562:Benzimidazoles; D002070:Butadienes; D016875:tau Proteins; C031000:benzimidazole