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

Kathleen Ran,Anil V Nair,Jing Yang,Biyue Zhu,Chongzhao Ran

doi:10.3390/molecules25040863

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.

Highlights

The current, prevailing understanding of Alzheimer’s disease (AD) pathology is rooted in the amyloid hypothesis and Tau hypothesis
Regardless, imaging Aβ plaques remains a crucial aspect of such studies and finding effective imaging tools can help clarify the pathological role of Aβ plaques in AD
We investigated the staining quality of Aβ plaque achieved by CRANAD-28 compared to that achieved by Thioflavin S, the currently gold standard for

Summary

Introduction

The current, prevailing understanding of Alzheimer’s disease (AD) pathology is rooted in the amyloid hypothesis and Tau hypothesis. The amyloid hypothesis attributes cognitive decline and neurodegeneration to the accumulation and deposition of Aβ peptides within the brain [1,2,3]. According to the amyloid hypothesis, Aβ peptide is the causative agent which instigates neurofibrillary tangle formation, neuron death, and vascular damage, culminating in the disease’s most visible symptom, dementia [1,4,5]. Deposits of Aβ peptides form Aβ plaques, which are the characteristic hallmarks of AD. The role of Aβ plaques in AD pathology has increasingly come under attack as.

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