Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Room 2301, Building 149, Charlestown, Boston, MA 02129, USA.
Center for systems biology, Program in Membrane, Biology, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Molecules. 2020 Feb 16;25(4):863. doi: 10.3390/molecules25040863.
CRANAD-28, a difluoroboron curcumin analogue, has been demonstrated in earlier reports to successfully label amyloid beta (Aβ) plaques for imaging both ex vivo and in vivo. CRANAD-28's imaging brightness, ability to penetrate the blood brain barrier, and low toxicity make the compound a potentially potent imaging tool in Alzheimer's research. In this study, the Aβ-labeling ability of CRANAD-28 was investigated in further detail using histological staining to assess different criteria, including stained Aβ plaque brightness, Aβ plaque size, and Aβ plaque number count. The results of this study demonstrated CRANAD-28 to be superior across all criteria assessed. Furthermore, CRANAD-28 and IBA-1 antibody were used to label Aβ-plaques and microglia respectively. Statistical analysis with Spearman regression revealed a statistically significant negative correlation between the size of labeled Aβ plaques and surrounding microglia density. This finding provides interesting insight into Aβ plaque and microglia dynamism in AD pathology and corroborates the findings of previous studies. In addition, we found that CRANAD-28 provided distinct spectral signatures for Aβs in the core and periphery of the plaques. Based on the study's results, CRANAD-28 could be considered as an alternative standard for imaging Aβ-plaques in future research studies.
CRANAD-28 是一种二氟硼化姜黄素类似物,早期的研究报告表明它能够成功地对淀粉样 β(Aβ)斑块进行成像,无论是在体外还是体内。CRANAD-28 的成像亮度、穿透血脑屏障的能力和低毒性使其成为阿尔茨海默病研究中一种有潜力的强大成像工具。在这项研究中,使用组织学染色进一步详细研究了 CRANAD-28 的 Aβ 标记能力,以评估不同的标准,包括染色 Aβ 斑块的亮度、Aβ 斑块的大小和 Aβ 斑块数量的计数。研究结果表明,CRANAD-28 在所有评估标准上均表现优异。此外,CRANAD-28 和 IBA-1 抗体分别用于标记 Aβ 斑块和小胶质细胞。使用 Spearman 回归的统计分析显示,标记的 Aβ 斑块的大小与周围小胶质细胞密度之间存在统计学上显著的负相关。这一发现为 AD 病理学中 Aβ 斑块和小胶质细胞的动态变化提供了有趣的见解,并证实了先前研究的结果。此外,我们发现 CRANAD-28 为斑块核心和周围的 Aβ 提供了独特的光谱特征。基于研究结果,CRANAD-28 可以被视为未来研究中 Aβ 斑块成像的替代标准。