Aβ plaque-selective NIR fluorescence probe to differentiate Alzheimer's disease from tauopathies.
Aβ plaque-selective NIR fluorescence probe to differentiate Alzheimer's disease from tauopathies.
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DOI：
10.1016/j.bios.2017.06.030
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发表时间：
2017-12-15
影响因子：
12.6
通讯作者：
Govindaraju T
中科院分区：
文献类型：
--
作者：
Rajasekhar K;Narayanaswamy N;Murugan NA;Viccaro K;Lee HG;Shah K;Govindaraju T
选择性检测和染色毒性淀粉样蛋白斑块，一个潜在的生物标志物存在于阿尔茨海默病（AD）的大脑是至关重要的临床诊断和监测AD疾病的进展。本文报道了一种基于香豆素-喹啉（CQ）共轭物的开启近红外（NIR）荧光探针，用于特异性检测β-淀粉样蛋白（Aβ）聚集体。CQ探针具有高灵敏度，在体外结合Aβ聚集体时表现出约100倍的荧光增强，量子产率提高。此外，与常用的硫磺素T相比，该探针对Aβ聚集体的结合亲和力（86 nM）高约10倍。最重要的是，与其他毒性蛋白质聚集体如tau、α-突触核蛋白（α-Syn）和胰岛淀粉样多肽（IAPP）相比，CQ探针对Aβ聚集体显示明确的选择性。此外，CQ对神经元细胞无毒，并显示出显著的血脑屏障通透性。值得注意的是，CQ染色人脑组织中的Aβ斑块超过共存的tau聚集体和神经元缠结（NFT），其与AD和tau蛋白病相关。这是区分AD与tau病理学和混合性痴呆的高度期望的属性。
Selective detection and staining of toxic amyloid plaques, a potential biomarker present in the Alzheimer’s disease (AD) brain is crucial for both clinical diagnosis and monitoring AD disease progression. Herein, we report a coumarin-quinoline (CQ) conjugate-based turn-on near-infrared (NIR) fluorescence probe for specific detection of β-amyloid (Aβ) aggregates. CQ probe is highly sensitive and exhibits ~100-fold fluorescence enhancement in vitro upon binding Aβ aggregates with enhanced quantum yield. Furthermore, the probe has ~10-fold higher binding affinity towards Aβ aggregates (86 nM) compared to commonly used Thioflavin T. Most importantly, CQ probe displays unambiguous selectivity towards Aβ aggregates compared to other toxic protein aggregates such as tau, α-synuclein (α-Syn) and islet amyloid polypeptide (IAPP). In addition, CQ is nontoxic to neuronal cells and shows significant blood brain barrier permeability. Remarkably, CQ stains Aβ plaques in human brain tissue over co-existing tau aggregates and neurofibrillary tangles (NFTs), which are associated in AD and tauopathies. This is a highly desirable attribute to distinguish AD from tau pathology and mixed dementia.
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