Department of Pharmacology, Tohoku University School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Mol Imaging Biol. 2014 Feb;16(1):19-27. doi: 10.1007/s11307-013-0667-2.
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.
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.
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.
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.
选择性可视化淀粉样蛋白-β 和 tau 蛋白沉积物将有助于了解阿尔茨海默病 (AD) 的病理生理学。在这里，我们介绍了一种新的荧光探针，它可以通过多光谱荧光成像技术来区分这两种沉积物。
使用新型荧光化合物对 AD 脑切片进行荧光光谱分析。使用 [(3)H]-PiB 进行竞争结合测定，以评估 BF-188 对合成淀粉样蛋白-β (Aβ) 和 tau 纤维的结合亲和力。
在 AD 脑切片中，BF-188 清晰地染色了 Aβ 和 tau 蛋白沉积物，具有不同的荧光光谱。体外结合实验表明，BF-188 与淀粉样蛋白-β 和 tau 纤维具有高亲和力（Ki < 10 nM）。此外，BF-188 在小鼠中表现出良好的血脑屏障通透性。
使用 BF-188 进行多光谱成像可能可用于选择性体内成像脑内 tau 沉积物以及淀粉样蛋白-β。
