In vivo detection of tau fibrils and amyloid β aggregates with luminescent conjugated oligothiophenes and multiphoton microscopy
In vivo detection of tau fibrils and amyloid β aggregates with luminescent conjugated oligothiophenes and multiphoton microscopy
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DOI：
10.1186/s40478-019-0832-1
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发表时间：
2019-11-08
影响因子：
7.1
通讯作者：
Bacskai, Brian J.
中科院分区：
文献类型：
--
作者：
Calvo-Rodriguez, Maria;Hou, Steven S.;Bacskai, Brian J.
检测淀粉样β沉积和神经纤维缠结是理解这些病理机制的关键，这两个都是阿尔茨海默病(AD)的特征。发光共轭低聚硫酚(LCoS)使这些蛋白质聚集体的荧光成像成为可能。使用LCoS和多光子显微镜，分别在活体内标记单个缠结和淀粉样β沉积，并在牛角病和脑淀粉样变性的小鼠模型中纵向成像。重要的是，LCO HS-84的发射落在光谱的绿色区域，首次允许在单次静脉注射后对缠绕动力学进行纵向成像。此外，LCO HS-169的发射落在光谱的红色区域，成功地标记了淀粉样β沉积，允许与发射落在光谱的绿色区域的其他记者进行多路复用。总之，这种方法可以为利用多光子显微镜对AD病理以及与蛋白质聚集相关的其他神经退行性疾病的小鼠模型进行体内纵向成像提供一种新的方法。
The detection of amyloid beta deposits and neurofibrillary tangles, both hallmarks of Alzheimer's disease (AD), is key to understanding the mechanisms underlying these pathologies. Luminescent conjugated oligothiophenes (LCOs) enable fluorescence imaging of these protein aggregates. Using LCOs and multiphoton microscopy, individual tangles and amyloid beta deposits were labeled in vivo and imaged longitudinally in a mouse model of tauopathy and cerebral amyloidosis, respectively. Importantly, LCO HS-84, whose emission falls in the green region of the spectrum, allowed for the first time longitudinal imaging of tangle dynamics following a single intravenous injection. In addition, LCO HS-169, whose emission falls in the red region of the spectrum, successfully labeled amyloid beta deposits, allowing multiplexing with other reporters whose emission falls in the green region of the spectrum. In conclusion, this method can provide a new approach for longitudinal in vivo imaging using multiphoton microscopy of AD pathologies as well as other neurodegenerative diseases associated with protein aggregation in mouse models.