Use of a Benzimidazole Derivative BF-188 in Fluorescence Multispectral Imaging for Selective Visualization of Tau Protein Fibrils in the Alzheimer's Disease Brain

Selective visualization of amyloid-beta 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. Fluorescence spectral analysis was performed using AD brain sections stained with novel fluorescence compounds. Competitive binding assay using [H-3]-PiB was performed to evaluate the binding affinity of BF-188 for synthetic amyloid-beta (A beta) and tau fibrils. In AD brain sections, BF-188 clearly stained A beta and tau protein deposits with different fluorescence spectra. In vitro binding assays indicated that BF-188 bound to both amyloid-beta and tau fibrils with high affinity (K (i) < 10 nM). In addition, BF-188 showed an excellent blood-brain barrier permeability in mice. Multispectral imaging with BF-188 could potentially be used for selective in vivo imaging of tau deposits as well as amyloid-beta in the brain.