Aggregated species of amyloid-β (Aβ) are one of the pathological hallmarks in Alzheimer’s disease (AD), and ligands that selectively target different Aβ deposits are of great interest. In this study, fluorescent thiophene-based ligands have been used to illustrate the features of different types of Aβ deposits found in AD brain tissue. A dual-staining protocol based on two ligands, HS-276 and LL-1, with different photophysical and binding properties, was developed and applied on brain tissue sections from patients affected by sporadic AD or familial AD associated with the PSEN1 A431E mutation. When binding to Aβ deposits, the ligands could easily be distinguished for their different fluorescence, and distinct staining patterns were revealed for these two types of AD. In sporadic AD, HS-276 consistently labeled all immunopositive Aβ plaques, whereas LL-1 mainly stained cored and neuritic Aβ deposits. In the PSEN1 A431E cases, each ligand was binding to specific types of Aβ plaques. The ligand-labeled Aβ deposits were localized in distinct cortical layers, and a laminar staining pattern could be seen. Biochemical characterization of the Aβ aggregates in the individual layers also showed that the variation of ligand binding properties was associated with certain Aβ peptide signatures. For the PSEN1 A431E cases, it was concluded that LL-1 was binding to cotton wool plaques, whereas HS-276 mainly stained diffuse Aβ deposits. Overall, our findings showed that a combination of ligands was essential to identify distinct aggregated Aβ species associated with different forms of AD.

中文翻译：

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基于噻吩的配体用于阿尔茨海默病中不同 Aβ 病理学的特异性分配

β 淀粉样蛋白 (Aβ) 的聚集是阿尔茨海默病 (AD) 的病理标志之一，选择性靶向不同 Aβ 沉积物的配体引起了人们的极大兴趣。在这项研究中，基于荧光噻吩的配体已被用来说明 AD 脑组织中发现的不同类型 Aβ 沉积物的特征。基于具有不同光物理和结合特性的两种配体 HS-276 和 LL-1 的双染色方案被开发并应用于受PSEN1 A431E突变相关的散发性 AD 或家族性 AD 患者的脑组织切片。当与 Aβ 沉积物结合时，可以很容易地区分配体的不同荧光，并且揭示了这两种类型的 AD 的不同染色模式。在散发性 AD 中，HS-276 一致地标记所有免疫阳性 Aβ 斑块，而 LL-1 主要对核心和神经炎 Aβ 沉积物进行染色。在PSEN1 A431E病例中，每种配体都与特定类型的 Aβ 斑块结合。配体标记的 Aβ 沉积物位于不同的皮质层中，并且可以看到层状染色图案。各个层中 Aβ 聚集体的生化特征还表明，配体结合特性的变化与某些 Aβ 肽特征相关。对于PSEN1 A431E病例，得出的结论是 LL-1 与棉绒斑块结合，而 HS-276 主要染色弥漫性 Aβ 沉积物。总的来说，我们的研究结果表明，配体的组合对于识别与不同形式的 AD 相关的不同聚集 Aβ 种类至关重要。