3D Visualization of the Temporal and Spatial Spread of Tau Pathology Reveals Extensive Sites of Tau Accumulation Associated with Neuronal Loss and Recognition Memory Deficit in Aged Tau Transgenic Mice
3D Visualization of the Temporal and Spatial Spread of Tau Pathology Reveals Extensive Sites of Tau Accumulation Associated with Neuronal Loss and Recognition Memory Deficit in Aged Tau Transgenic Mice
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DOI：
10.1371/journal.pone.0159463
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发表时间：
2016-07-28
期刊：
影响因子：
3.7
通讯作者：
Duff, Karen E.
中科院分区：
文献类型：
--
作者：
Fu, Hongjun;Hussaini, S. Abid;Duff, Karen E.
使用 iDISCO+ 的 3D 体积成像用于观察小鼠模型大脑深层结构中 tau 病理学的空间和时间进展，该模型概括了阿尔茨海默病 (AD) 的最早阶段。在长达 34 个月的四个时间点对 Tau 蛋白病理学进行了比较，因为它沿着解剖学上相连的路线扩散到海马结构并进入新皮质。 Tau 病理学与显着的神经胶质增生相关。没有观察到神经胶质细胞摄取和积累 tau 蛋白的证据。神经元细胞似乎确实内化了 tau，包括在海马外区域，因为一小部分积累了人 tau 蛋白的细胞不表达可检测水平的人 tau mRNA。在最古老的时间点，内嗅皮质 (EC) 中成熟的 tau 病理学与显着的细胞损失相关。与人类 AD 一样，EC 中成熟的 tau 病理学和新皮质中 tau 病理学的存在与认知障碍相关。 3D 体积成像是一种理想的技术，可以在疾病进展模型中轻松监测病理学随时间的传播。
3D volume imaging using iDISCO+ was applied to observe the spatial and temporal progression of tau pathology in deep structures of the brain of a mouse model that recapitulates the earliest stages of Alzheimer's disease (AD). Tau pathology was compared at four timepoints, up to 34 months as it spread through the hippocampal formation and out into the neocortex along an anatomically connected route. Tau pathology was associated with significant gliosis. No evidence for uptake and accumulation of tau by glia was observed. Neuronal cells did appear to have internalized tau, including in extrahippocampal areas as a small proportion of cells that had accumulated human tau protein did not express detectible levels of human tau mRNA. At the oldest timepoint, mature tau pathology in the entorhinal cortex (EC) was associated with significant cell loss. As in human AD, mature tau pathology in the EC and the presence of tau pathology in the neocortex correlated with cognitive impairment. 3D volume imaging is an ideal technique to easily monitor the spread of pathology over time in models of disease progression.