Differentiating Aβ40 and Aβ42 with a small molecule fluorescence probe


Yang J, Zhu B, Yin W, Han Z, Zheng C, Wang P, Ran C. Differentiating Aβ40 and Aβ42 with a small molecule fluorescence probe. Chemical Science. 2020;11 :5238-5245 .


Differentiating amyloid beta (Ab) subspecies Ab40 and Ab42 has long been considered as an impossible mission with small-molecule probes. In this report, based on recently published structures of Ab fibrils, we designed iminocoumarin-thiazole (ICT) fluorescence probes to differentiate Ab40 and Ab42, among which Ab42 has much higher neurotoxicity. We demonstrated that ICTAD-1 robustly responds to Ab fibrils, evidenced by turn-on fluorescence intensity and red-shifting of emission peaks. Remarkably, ICTAD-1 showed different spectra towards Ab40 and Ab42 fibrils. In vitro results demonstrated that ICTAD-1 could be used to differentiate Ab40/42 in solutions. Moreover, our data revealed that ICTAD-1 could be used to separate Ab40/42 components in plaques of AD mouse brain slides. In addition, two-photon imaging suggested that ICTAD-1 was able to cross the BBB and label plaques in vivo. Interestingly, we observed that ICTAD-1 was specific toward plaques, but not cerebral amyloid angiopathy (CAA) on brain blood vessels. Given Ab40 and Ab42 species have significant differences of neurotoxicity, we believe that ICTAD-1 can be used as an important tool for basic studies and has the potential to provide a better diagnosis in the future.

Last updated on 08/16/2020