Different types of deposits comprised of amyloid-β (Aβ) peptides are one of the pathological hallmarks of Alzheimer’s disease (AD) and novel methods that enable identification of a diversity of Aβ deposits during the AD continuum are essential for understanding the role of these aggregates during the pathogenesis. Herein, different combinations of five fluorescent thiophene-based ligands were used for detection of Aβ deposits in brain tissue sections from transgenic mouse models with aggregated Aβ pathology, as well as brain tissue sections from patients affected by sporadic or dominantly inherited AD. When analyzing the sections with fluorescence microscopy, distinct ligand staining patterns related to the transgenic mouse model or to the age of the mice were observed. Likewise, specific staining patterns of different Aβ deposits were revealed for sporadic versus dominantly inherited AD, as well as for distinct brain regions in sporadic AD. Thus, by using dual-staining protocols with multiple combinations of fluorescent ligands, a chronological and spatial histological designation of different Aβ deposits could be achieved. This study demonstrates the potential of our approach for resolving the role and presence of distinct Aβ aggregates during the AD continuum and pinpoints the necessity of using multiple ligands to obtain an accurate assignment of different Aβ deposits in the neuropathological evaluation of AD, as well as when evaluating therapeutic strategies targeting Aβ aggregates.

中文翻译：

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双配体荧光显微镜可对不同的淀粉样蛋白β沉积物进行时间学和空间组织学分配


由淀粉样蛋白β （Aβ） 肽组成的不同类型的沉积物是阿尔茨海默病 （AD） 的病理标志之一，能够在 AD 连续体中识别各种 Aβ 沉积物的新方法对于了解这些聚集体在发病机制中的作用至关重要。在此，使用五种基于噻吩的荧光配体的不同组合来检测具有聚集 Aβ 病理学的转基因小鼠模型的脑组织切片中的 Aβ 沉积物，以及散发性或显性遗传性 AD 患者的脑组织切片中的 Aβ 沉积物。当用荧光显微镜分析切片时，观察到与转基因小鼠模型或小鼠年龄相关的不同配体染色模式。同样，散发性与显性遗传性 AD 以及散发性 AD 中不同脑区的不同 Aβ 沉积物的特异性染色模式也被揭示出来。因此，通过使用具有荧光配体多种组合的双重染色方案，可以实现不同 Aβ 沉积物的时间顺序和空间组织学名称。这项研究证明了我们的方法在 AD 连续体中解决不同 Aβ 聚集体的作用和存在的潜力，并指出了在 AD 的神经病理学评估以及评估针对 Aβ 聚集体的治疗策略时，使用多个配体来准确分配不同 Aβ 沉积物的必要性。