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

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.

The Role of Microbiome in Brain Development and Neurodegenerative Diseases

“…Lu and colleagues (2012) identified a series of boron-containing compounds that act as Aβ aggregation inhibitors ( 3 ), antioxidants, and metal chelators in the treatment of Alzheimer’s disease [ 183 ]. Curcumin is currently being studied for its potential to treat a variety of cancers, as well as to prevent neuronal damage in Alzheimer’s disease.…”

“…Studies have also shown that CRANAD-28 ( 5 ), a difluoroboron curcumin derivative, may successfully identify amyloid-beta plaques for imaging both ex vivo and in vivo. The imaging brightness of CRANAD-28 ( 5 ), as well as its ability to pass the blood–brain barrier and low toxicity, making it a potentially useful imaging tool in Alzheimer’s research [ 183 ]. Given Alzheimer’s disease’s complex nature and pathophysiology, treatment techniques are being developed to integrate the benefits of each single-target therapy into a single molecule.…”

Curcumin Scaffold as a Multifunctional Tool for Alzheimer’s Disease Research

“…These curcumin analogues can detect Aβs in vitro and in vivo; however, the probes always have low quantum yield (QY). Ran et al substituted the phenyl rings with pyrazoles to improve the brightness of these probes in order to overcome their low QY limitation [59,69]. CRANAD-28 has a high QY (Φ = 32%) in PBS as expected.…”

Der Lebensmittelfarbstoff Curcumin (E 100)

“…Ihre Farbe kann dabei durch ihre Arylsubstituenten von Gelb bis Rot variiert werden. Gleichzeitig sind diese 4,6-Diaryl-1,3,2-dioxaborine intensiv fluoreszenzfähig und eignen sich daher als Laserfarbstoffe [13] oder Fluoreszenzsonden [14]. Beim Übergang zu 4,6-Bis-styryl-1,3,2-dioxabonrinen des Formeltyps 16 kann das langwellige Absorptionsmaximum bei geeigneter Substitution bis in das nahe IR-Gebiet verschoben werden, so dass entspr.…”