AIMS Histological analysis of brain tissue samples provides valuable information about the pathological processes leading to common neurodegenerative disorders. In this context, the development of novel high-resolution imaging approaches is a current challenge in neuroscience. METHODS To this end, we used a recent super-resolution imaging technique called STochastic Optical Reconstruction Microscopy (STORM) to analyse human brain sections. We combined STORM cell imaging protocols with neuropathological techniques to image cryopreserved brain samples from control subjects and patients with neurodegenerative diseases. RESULTS This approach allowed us to perform 2D-, 3D- and two-colour-STORM in neocortex, white matter and brainstem samples. STORM proved to be particularly effective at visualizing the organization of dense protein inclusions and we imaged with a <50 nm resolution pathological aggregates within the central nervous system of patients with Alzheimer's disease, Parkinson's disease, Lewy body dementia, and fronto-temporal lobar degeneration. Aggregated Aβ branches appeared reticulated and cross-linked in the extracellular matrix, with widths from 60 to 240 nm. Intraneuronal Tau and TDP-43 inclusions were denser, with a honeycomb pattern in the soma and a filamentous organization in the axons. Finally, STORM imaging of α-synuclein pathology revealed the internal organization of Lewy bodies that could not be observed by conventional fluorescence microscopy. CONCLUSIONS STORM imaging of human brain samples opens further gates to a more comprehensive understanding of common neurological disorders. The convenience of this technique should open a straightforward extension of its application for super-resolution imaging of the human brain, with promising avenues to current challenges in neuroscience.

中文翻译：

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随机光学重建显微镜（STORM）揭示了人脑中病理聚集体的纳米级组织


目的 脑组织样本的组织学分析提供了有关导致常见神经退行性疾病的病理过程的宝贵信息。在这种背景下，开发新型高分辨率成像方法是神经科学当前的挑战。方法为此，我们使用了一种最新的超分辨率成像技术，称为随机光学重建显微镜（STORM）来分析人脑切片。我们将 STORM 细胞成像方案与神经病理学技术相结合，对来自对照受试者和神经退行性疾病患者的冷冻保存的大脑样本进行成像。结果这种方法使我们能够在新皮质、白质和脑干样本中进行 2D、3D 和双色风暴。事实证明，STORM 在可视化致密蛋白质内含物的组织方面特别有效，我们对阿尔茨海默病、帕金森病、路易体痴呆和额颞叶变性患者的中枢神经系统内的病理聚集体进行了 <50 nm 分辨率的成像。聚集的 Aβ 分支在细胞外基质中呈网状和交联，宽度为 60 至 240 nm。神经元内 Tau 和 TDP-43 内含物更致密，胞体中呈蜂窝状，轴突中呈丝状组织。最后，α-突触核蛋白病理学的 STORM 成像揭示了传统荧光显微镜无法观察到的路易体的内部组织。结论 人脑样本的风暴成像为更全面地了解常见神经系统疾病打开了新的大门。 这项技术的便利性应该能够直接扩展其在人脑超分辨率成像方面的应用，并为应对当前神经科学挑战提供有希望的途径。