Historically, in Alzheimer's disease research, a lot of attention has been paid to the development of highly selective fluorophores for beta amyloid plaques. With a shift in the understanding of the disease and the importance of a network of cross-talk interactions, the development of small-molecule fluorescent dyes with high selectivity for (hyperphosphorylated) tau protein aggregates in neurofibrillary tangles has been gaining increasing attention. Fluorescent dyes for the selective labelling of tau aggregates in histological AD brain sections have been described, spanning the entire visible range of the electromagnetic spectrum. Despite the relatively early stages of the development of the field, a large diversity in probe architectures has been reported. Importantly, a handful of near-infrared-emissive dyes have been described as well, and some of these have exhibited good pharmacological profiles, with a significant blood–brain-barrier permeability, and a demonstrated ability to label tau tangles in vivo in small-animal models of Alzheimer's disease and other tauopathies. The developments summarized in the current work are expected to aid the unravelling of the diverse set of players in the etiology of Alzheimer's disease. In this tutorial review, we seek to provide the reader with an overview of the most important recent developments and hope to provide some guidelines for the design of future probes.

中文翻译：

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阐明tau蛋白聚集：开发高选择性荧光团的进展

从历史上看，在阿尔茨海默氏病研究中，人们对开发高度选择性的荧光团用于β淀粉样蛋白斑块已给予了很多关注。随着人们对疾病的理解和交叉互动网络的重要性的转移，对神经原纤维缠结中的（超磷酸化）tau蛋白聚集体具有高选择性的小分子荧光染料的开发日益受到关注。已经描述了用于在组织学AD脑切片中选择性标记tau聚集体的荧光染料，其跨电磁光谱的整个可见范围。尽管该领域的发展处于相对较早的阶段，但是已经报道了探针结构的多样性。重要的是，还描述了几种近红外发射染料，在阿尔茨海默氏病和其他疾病的小动物模型中进行体内实验。预期当前工作中总结的发展将有助于阐明阿尔茨海默氏病病因的各种参与者。在本教程的复习中，我们试图为读者提供最重要的最新进展的概述，并希望为将来的探针设计提供一些指导。