Probe development for systemic molecular imaging of Alzheimer’s disease

Citation:

Ran C. Probe development for systemic molecular imaging of Alzheimer’s disease, in World Molecular Imaging Congress, 2016, Sept.11-14. New York ; Working Paper.

Abstract:

Molecule imaging is an indispensible tool for diagnosis, treatment and basic mechanism studies. For a specific disease, the majority of research has been focusing on a single-biomarker imaging, which is particularly important for the purpose of diagnosis. However, given the complex nature of most diseases, systemic molecular imaging (SYMI) of multiple biomarkers of a single disease can be crucial for understanding its mechanism, and for designing more efficient therapeutics. 

 

Alzheimer’s disease (AD) is a multi-facet neurodegenative disease with multi-dimensional biomarkers. If the biomarkers of AD are considered in a multi-dimensional space, each category of biomarkers could be considered as one coordination axis. Amyloid beta (Ab) deposits and tau tangles are the most prominent pathological hallmarks of AD, and Ab and tau species respectively represent two essential axis of biomarkers of AD. It is also well accepted that oxidative stress is highly associated with AD, and reactive oxygen species (ROS) could also be considered as another important biomarker dimension of AD. Considering AD biomarkers in a three-dimensional (3D) space, Ab, tau and ROS could be considered as x, y, z-coordination axis correspondingly.

 

This presentation will focus on our recent results from our laboratory in systemic molecular imaging of AD, particularly on the biomarker dimensions of Aβs and ROS.  On the axis of Aβ, multiple sub-species, including insoluble and soluble Aβs consist a complex family of biomarkers. Currently, it is not clear which sub-species could serve as a better biomarker for AD severity and progression. In the past few years, our research has been concentrated on three-phase development of  “smart” NIRF probes for various Aβ species. In phase (I), we developed a new family of NIR fluorescent dyes (termed CRANAD-X) for insoluble Aβs. In phase (II), we have successfully developed NIRF probes for both soluble and insoluble Aβ species. In phase (III) we have concentrated our efforts on developing imaging probes that are selective for soluble Aβs. On the ROS axis, we have first designed NIRF probes for detection of H2O2, and then designed NIRF probes that are sensitive to various ROS. Our data showed the excellent correlation between ROS levels and the progression of AD. Taken together, with imaging probes for different dimensions of AD biomarkers, we believe that systemic molecular imaging will be a vital approach for understanding the complexity of AD, and for efficiently assisting AD drug development.

 

Reference

    1. Ran C, Xu X, Raymond SB, Ferrara BJ, Neal K, Bacskai BJ, Medarova Z, Moore A, J. Amer. Chem. Soc., 2009,131(42):15257-61.
    2. Zhang X, Tian Y, Li Z, Tian X, Sun H, Liu H, Moore A, Ran C.*, J. Amer. Chem. Soc., 2013, 135(44):16397-409.
    3. Zhang X, Tian Y, Yuan P, Li Y., Yaseen MA, Grutzendler J, Moore A, Ran C.*, Chem. Commun., 2014, 50(78):11550-3.
    4. Zhang X, Tian Y, Zhang C, Tian X, Ross AW, Moir RD, Sun H, Tanzi RE, Moore A, and Ran C*, Proc. Natl. Aca Sci. USA, 2015, 112(31):9734-9.