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  2. CRANAD-28: A Robust Fluorescent Compound for Visualization of Amyloid Beta Plaques

CRANAD-28: A Robust Fluorescent Compound for Visualization of Amyloid Beta Plaques

  • Molecules. 2020 Feb 16;25(4):863. doi: 10.3390/molecules25040863.
Kathleen Ran 1 Jing Yang 1 Anil V Nair 2 Biyue Zhu 1 3 Chongzhao Ran 1
Affiliations

Affiliations

  • 1 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.
  • 2 Center for systems biology, Program in Membrane, Biology, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • 3 West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Abstract

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.

Keywords

amyloid beta; fluorescent probe; plaque staining.

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