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Academic report: Probe development for systemic molecular imaging of Alzheimer’s disease

Molecule imaging has been an indispensible tool for diagnosis, pathology investigation and basic mechanism studies in the past decades. For a specific disease, majority of research has been focusing on single-biomarker imaging, which is particularly important for the purpose of diagnosis. However, given the complex nature of diseases, systemic molecular imaging (SYMI) of multi-biomarkers of a single disease can be crucial for understanding the disease, and better designing therapeutics. Alzheimer’s disease (AD) is a multi-facet neurodegenerative disease, and its biomarkers are also multi-dimensional. Amyloid beta (Aβ) deposits and tau tangles are the most typical pathological hallmarks of AD, and Aβ species and tau have been considered to be essential dimensions for imaging AD. However, it is very likely that other biomarkers also highly correlated with the impaired cognitive functions of AD patients. Among them, reactive oxygen species (ROS) have been widely believed to be an important dimension for AD imaging. In this presentation, I will share our recent results on systemic molecular imaging of AD, particularly on the dimensions of Aβs and ROS. On the dimension of Aβ species, it has been intensely debated which sub-species, including insoluble Aβs and soluble Aβs, could be better biomarkers for AD severity and progression. In the past few years, our research has been concentrated on a trilogy of developing “smart” NIRF probes for various Aβ species. For this trilogy, in episode (I) we have effectively developed NIRF probes for insoluble Aβs. In this episode, we have invented a brand-new family of NIR fluorescent dyes CRANAD-X, and some of them are “smart” probes for the insoluble Aβs.

In recent years, mounting evidence indicates that the soluble Aβs are probably the most neurotoxic species. However, most of the current imaging probes are primarily sensitive for insoluble Aβs. In episode (II), we have successfully developed NIRF probes for both soluble and insoluble Aβ species, and we believe that these probes may have the potential to monitoring the full course of the amyloidosis of AD. For better understanding AD pathology, selectively imaging of the most neurotoxic soluble Aβs is very necessary. In episode (III), we have concentrated our efforts on developing imaging probes selective for soluble Aβs, thus to accomplish early detecting of AD pathology. For the ROS dimension, in the past years, we also have designed several probes for imaging ROS and H2O2. I will present data to show the correlation of ROS level and the progression of AD.