Laboratory of Neural Plasticity and Regeneration, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
J Neuropathol Exp Neurol. 2010 Apr;69(4):405-14. doi: 10.1097/NEN.0b013e3181d709eb.
The study aimed to characterize curcumin (CCM) (fluorescent yellow curry pigment) labeling of neuronal fibrillar tau inclusions (FTIs) in representative cases of 3 main tauopathies: Alzheimer disease (AD), progressive supranuclear palsy, and Pick disease. After identification of FTIs in hematoxylin and eosin-stained brain sections, sequential labeling and signal colocalization image analysis were used to compare CCM with thioflavine S (ThS), monoclonal antibody AT8 immunofluorescence, and Gallyas silver staining by visualizing the same FTIs. Curcumin preference for specific tau isoforms was tested with 3-repeat tau and 4-repeat tau isoform-specific immunofluorescence. Curcumin proved highly comparable to ThS and Gallyas staining in its detection of FTIs. When comparing CCM with AT8, ThS, and Gallyas staining in AD and progressive supranuclear palsy, 3 types of neuronal tau deposits were observed: nonfibrillar intracellular material labeled only with AT8, fibrillar intracellular inclusions labeled by all the methods, and fibrillar extracellular FTIs labeled with CCM, ThS, and Gallyas staining but not with AT8. Although CCM labeling overlapped with both 3-repeat tau and 4-repeat tau in AD, it did not label 3-repeat tau FTIs in Pick disease probably because of their different ultrastructural characteristics. In summary, CCM fluorescence reliably detected neuronal FTIs in AD and progressive supranuclear palsy and surpassed AT8 immunolabeling in visualizing later stages of FTIs, including ghost tangles. These results provide the basis for potential future applications of CCM binding of tau aggregates in diagnostic pathology and in vivo.
本研究旨在对 3 种主要 tau 病（阿尔茨海默病（AD）、进行性核上性麻痹和皮克病）的代表性病例中的神经元纤维状 tau 包涵体（FTIs）进行特征分析。在苏木精和伊红染色脑切片中鉴定 FTIs 后，使用顺序标记和信号共定位图像分析来比较 CCM 与硫黄素 S（ThS）、单克隆抗体 AT8 免疫荧光和 Gallyas 银染色，以可视化相同的 FTIs。通过使用 3 重复 tau 和 4 重复 tau 亚型特异性免疫荧光来测试 CCM 对特定 tau 亚型的偏好性。CCM 在检测 FTIs 方面与 ThS 和 Gallyas 染色高度可比。在 AD 和进行性核上性麻痹中比较 CCM 与 AT8、ThS 和 Gallyas 染色时，观察到 3 种神经元 tau 沉积物：仅用 AT8 标记的非纤维状细胞内物质、用所有方法标记的纤维状细胞内包涵体以及用 CCM、ThS 和 Gallyas 染色标记的纤维状细胞外 FTIs，但不能用 AT8 标记。虽然 CCM 标记与 AD 中的 3 重复 tau 和 4 重复 tau 均重叠，但它不能标记 Pick 病中的 3 重复 tau FTIs，可能是因为它们具有不同的超微结构特征。总之，CCM 荧光可靠地检测了 AD 和进行性核上性麻痹中的神经元 FTIs，并在可视化 FTIs 的后期阶段（包括幽灵缠结）方面超过了 AT8 免疫标记。这些结果为 CCM 结合 tau 聚集物在诊断病理学和体内的潜在未来应用提供了基础。
