Enhancing Lateral Resolution Using Two-Colour Direct Stochastic Optical Reconstruction Microscopy to Unravel Synaptic Tau Pathology in Alzheimer's Disease.

IF 3.4 2区医学 Q1 CLINICAL NEUROLOGY

Neuropathology and Applied Neurobiology Pub Date : 2025-04-01 DOI:10.1111/nan.70010

Érika Sánchez-Aced, Borja Moya-Llamas, Joaquim Aumatell Escabias, Soraya Torres, Martí Colom-Cadena, Jordi Pegueroles, Cristian de Quintana-Schmidt, Àlex Bayés, Laura Molina-Porcel, Iban Aldecoa, Olivia Belbin, Juan Fortea, Tara Spires-Jones, Sílvia Pujals, Sònia Sirisi, Alberto Lleó

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引用次数: 0

Abstract

Aims: In Alzheimer's disease (AD), the pathological accumulation of tau in synapses contributes to synapse dysfunction and loss. However, the small and complex structure of synapses limits the investigation when using conventional techniques. In this work, we describe the combination of array tomography (AT) with two-colour direct stochastic optical reconstruction microscopy (dSTORM) to enhance lateral resolution for resolving synaptic terminals in human postmortem brain.

Methods: We applied this combination to study synapses in brain samples (from biopsy and postmortem) from healthy subjects and pathological synaptic tau (aggregates and oligomers) in samples from AD patients.

Results: AT combined with dSTORM allowed the characterisation of the orientation and shape of the synaptic terminals and the synaptic cleft. In addition, this combination confirmed the presence of oligomeric tau in synaptic terminals in AD.

Conclusions: Overall, we found that the combination of AT and two-colour dSTORM provides optimal resolution to detect pathological synaptic tau and its spatial relationship with presynaptic and postsynaptic terminals.

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利用双色直接随机光学重建显微镜增强横向分辨率揭示阿尔茨海默病突触Tau病理。

目的：在阿尔茨海默病（AD）中，突触中tau的病理积累导致突触功能障碍和丧失。然而，突触的小而复杂的结构限制了传统技术的研究。在这项工作中，我们描述了阵列断层扫描（AT）与双色直接随机光学重建显微镜（dSTORM）的结合，以提高解析人类死后大脑突触终端的侧向分辨率。方法：我们应用这种组合来研究健康受试者脑样本中的突触（来自活检和死后）和AD患者样本中的病理突触tau（聚集体和低聚物）。结果：AT联合dSTORM可以表征突触末梢和突触间隙的方向和形状。此外，这种结合证实了寡聚tau在AD的突触末端的存在。结论：总的来说，我们发现结合AT和双色dSTORM提供了最佳的分辨率来检测病理突触tau及其与突触前和突触后末端的空间关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropathology and Applied Neurobiology 医学-病理学

CiteScore

8.20

自引率

2.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Neuropathology and Applied Neurobiology is an international journal for the publication of original papers, both clinical and experimental, on problems and pathological processes in neuropathology and muscle disease. Established in 1974, this reputable and well respected journal is an international journal sponsored by the British Neuropathological Society, one of the world leading societies for Neuropathology, pioneering research and scientific endeavour with a global membership base. Additionally members of the British Neuropathological Society get 50% off the cost of print colour on acceptance of their article.