Spatial characterization of tangle-bearing neurons and ghost tangles in the human inferior temporal gyrus with three-dimensional imaging.
Spatial characterization of tangle-bearing neurons and ghost tangles in the human inferior temporal gyrus with three-dimensional imaging.
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DOI：
10.1093/braincomms/fcad130
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发表时间：
2023
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
对死后人体组织的研究提供了对病理过程的深入了解，但本质上受到实际考虑的限制，这些考虑限制了组织可以被检查的规模，以及组织仅反映连续疾病过程中的一个时间点的明显问题。我们通过将新的组织清除技术应用于人类大脑的整个皮层区域来解决这个问题，这使得在整个皮层厚度的深度上可以监视数十万个神经元。这种方法允许检测在标准5微米厚的石蜡切片中可能难以检测的“罕见”事件。例如，已经确定神经元缠结开始于神经元内，并且最终，在至少一些情况下，甚至在神经元已经死亡之后，仍然存在于脑中。这些被称为“幽灵纠缠”，这个术语恰当地暗示了它们“很难看到”的短暂特性。我们开始寻找鬼缠结作为一个例子的权力的组织清除/图像分析技术，以检测罕见的事件，并了解发生了什么事，在终点缠结的生活史。我们能够在来自患有严重阿尔茨海默病（Braak V-VI）的三名受试者的组织样品中鉴定8103个tau缠结、132 465个神经元和299 640个核，并且在来自没有显著tau病理学（Braak 0-I）的三名受试者的组织样品中鉴定4个tau缠结、200 447个神经元和462 715个核。在这些数据中，我们定位了57个幽灵缠结，这使得它们仅占观察到的总tau缠结的0.7%。我们发现幽灵缠结更可能在皮质层3和5（49/57）中发现，少数几个分散在其他层1，2，4和6中。这种发现罕见事件（如幽灵缠结）的能力，足以在统计上测试它们的分布，这证明了组织清除如何被用作研究大脑区域对病理学的选择性脆弱性或恢复力的强大工具。Zwang等人使用组织清除技术对跨人类颞下回皮质层的tau缠结、神经元和核进行成像和表征。大体积成像使得能够识别几十个鬼缠结，这是一种罕见的事件，并发现它们在皮层第三和第五层中更丰富。
Studies of post-mortem human tissue provide insight into pathological processes, but are inherently limited by practical considerations that limit the scale at which tissue can be examined, and the obvious issue that the tissue reflects only one time point in a continuous disease process. We approached this problem by adapting new tissue clearance techniques to an entire cortical area of human brain, which allows surveillance of hundreds of thousands of neurons throughout the depth of the entire cortical thickness. This approach allows detection of ‘rare’ events that may be difficult to detect in standard 5 micrometre-thick paraffin sections. For example, it is well established that neurofibrillary tangles begin within a neuron, and ultimately, in at least some instances, persist in the brain even after the neuron has died. These are referred to as ‘ghost tangles’, a term that appropriately implies their ‘difficult to see’ ephemeral qualities. We set out to find ghost tangles as one example of the power of the tissue clearance/image analysis techniques to detect rare events, and to learn what happens at the end-point of a tangle’s life history. We were able to identify 8103 tau tangles, 132 465 neurons and 299 640 nuclei in tissue samples from three subjects with severe Alzheimer’s disease (Braak V–VI) and 4 tau tangles, 200 447 neurons and 462 715 nuclei in tissue samples from three subjects with no significant tau pathology (Braak 0–I). Among these data, we located 57 ghost tangles, which makes them only 0.7% of the total tau tangles observed. We found that ghost tangles are more likely to be found in cortical layers 3 and 5 (49/57), with a select few scattered across other layers 1, 2, 4 and 6. This ability to find rare events, such as ghost tangles, in large enough quantities to statistically test their distribution exemplifies how tissue clearing can be used as a powerful tool for studying selective vulnerability or resilience to pathology across brain regions. Zwang et al. use tissue clearing techniques to image and characterize tau tangles, neurons, and nuclei across cortical layers of human inferior temporal gyrus. Imaging large volumes enabled the identification of dozens of ghost tangles, a rare event, and finds that they are more abundant in cortical layers three and five.
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DOI：
10.1002/alz.12321
发表时间：
2021-09
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Moloney CM;Lowe VJ;Murray ME
通讯作者：
Murray ME
DOI：
10.1038/s41583-019-0250-1
发表时间：
2020-02
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Ueda HR;Ertürk A;Chung K;Gradinaru V;Chédotal A;Tomancak P;Keller PJ
通讯作者：
Keller PJ
影响因子：
5.7
作者：
Rusch, Henriette;Brammerloh, Malte;Morawski, Markus
通讯作者：
Morawski, Markus
影响因子：
12.7
作者：
MERCKEN, M;VANDERMEEREN, M;GHEUENS, J
通讯作者：
GHEUENS, J
影响因子：
5.6
作者：
Mustaciosu, Cosmin Catalin;Banciu, Adela;Radu, Beatrice Mihaela
通讯作者：
Radu, Beatrice Mihaela