A peptide-based near-infrared fluorescence probe for dynamic monitoring senile plaques in Alzheimer＇s disease mouse model  

作　　者：Chen-Wei Wang Dou-Dou Nan Xin-Meng Wang zun-Ji Ke Guo-Jun Chen Jiang-Ning Zhou 

机构地区：[1]CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230026, China [2]Department of Biochemistry, Shanghai University of Traditional Chinese Medidne, Shanghai 201203, China [3]Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China

出　　处：《Science Bulletin》2017年第23期1593-1601,共9页科学通报（英文版）

基　　金：supported by the National Key Research and Development Program of China (2016YFC1305900);the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB02030001);the National Natural Science Foundation of China (91132304, 91432305)

摘　　要：In vivo monitoring neuropathological changes in Alzheimer＇s disease （AD） animal model is critical for drug development. Here, by integrating blood-brain barrier penetrable peptide, we have developed a peptide probe which based on angiopep-2. Angiopep-based probe exhibited high binding affinity to Aβ aggregates and labeled senile plaques in vivo. Remarkably, the in vivo near-infrared imaging data revealed that fluorescence signals of this probe were nearly 3-fold higher in the brains of 16-monthold APP/PSI transgenic mice compared to C57 mice and exhibited linear correlation with the senile plaques load process in 4-, 8-, 16-month-old APP/PSI transgenic mice. Moreover, senile plaques load was detected in vivo as early as 4 months of age that even at the very beginning of plaques developed in APP/PS1 transgenic mice. Taken together, this novel peptide-based probe achieved dynamic monitoring senile plaques in APP/PS1 transgenic mice and have been ready to use in drug development in AD mouse model.In vivo monitoring neuropathological changes in Alzheimer's disease(AD) animal model is critical for drug development. Here, by integrating blood-brain barrier penetrable peptide, we have developed a peptide probe which based on angiopep-2. Angiopep-based probe exhibited high binding affinity to Ab aggregates and labeled senile plaques in vivo. Remarkably, the in vivo near-infrared imaging data revealed that fluorescence signals of this probe were nearly 3-fold higher in the brains of 16-monthold APP/PS1 transgenic mice compared to C57 mice and exhibited linear correlation with the senile plaques load process in 4-, 8-, 16-month-old APP/PS1 transgenic mice. Moreover, senile plaques load was detected in vivo as early as 4 months of age that even at the very beginning of plaques developed in APP/PS1 transgenic mice. Taken together, this novel peptide-based probe achieved dynamic monitoring senile plaques in APP/PS1 transgenic mice and have been ready to use in drug development in AD mouse model.

关 键 词：Alzlaelmer＇s diseaseSenile plaquesAmyloid-β LRP-1 Angiopep In vivo imaging AD animal model 

分 类 号：O657.3[理学—分析化学] R749.16[理学—化学]