阿尔茨海默病和非阿尔茨海默病 Tau 病中 Tau 病理学的高对比体内成像。

High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies.

机构信息

National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; Department of Psychiatry, The Jikei University Graduate School of Medicine, Tokyo 105-8461, Japan.

National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.

出版信息

Neuron. 2021 Jan 6;109(1):42-58.e8. doi: 10.1016/j.neuron.2020.09.042. Epub 2020 Oct 29.

DOI:10.1016/j.neuron.2020.09.042

PMID:33125873

Abstract

A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick's disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.

摘要

一组放射性化学物质使阿尔茨海默病（AD）中的 tau 病理学能够进行体内正电子发射断层扫描（PET），尽管未能成功检测额颞叶变性（FTLD）tau 包涵体。在这里，我们生成了一种成像探针 PM-PBB3，用于捕获各种 tau 沉积物。体外检测证实了该化合物与 AD 和 FTLD 中的 tau 病变的反应性。我们还可以利用 PM-PBB3 对活体 tau 病模型进行光学/PET 成像。随后的临床 PET 研究显示，患病患者中 F-PM-PBB3 的结合增加，反映了皮质优势型 AD 和皮质基底节变性（PSP）tau 拓扑结构。值得注意的是，F-PM-PBB3 与 FTLD tau 包涵体的体内反应性得到了从 Pick 病、PSP 和皮质基底节变性患者脑活检中获得的 PET 扫描的支持，这些患者进行了 PET 扫描。最后，视觉检查 F-PM-PBB3-PET 图像有助于根据神经病理学基础上基于个体的方式识别 FTLD 的各种临床表型。