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A comparative study of dietary curcumin, nanocurcumin, and other classical amyloid-binding dyes for labeling and imaging of amyloid plaques in brain tissue of 5×-familial Alzheimer’s disease mice

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Abstract

Deposition of amyloid beta protein (Aβ) is a key component in the pathogenesis of Alzheimer’s disease (AD). As an anti-amyloid natural polyphenol, curcumin (Cur) has been used as a therapy for AD. Its fluorescent activity, preferential binding to Aβ, as well as structural similarities with other traditional amyloid-binding dyes, make it a promising candidate for labeling and imaging of Aβ plaques in vivo. The present study was designed to test whether dietary Cur and nanocurcumin (NC) provide more sensitivity for labeling and imaging of Aβ plaques in brain tissues from the 5×-familial AD (5×FAD) mice than the classical Aβ-binding dyes, such as Congo red and Thioflavin-S. These comparisons were made in postmortem brain tissues from the 5×FAD mice. We observed that Cur and NC labeled Aβ plaques to the same degree as Aβ-specific antibody and to a greater extent than those of the classical amyloid-binding dyes. Cur and NC also labeled Aβ plaques in 5×FAD brain tissues when injected intraperitoneally. Nanomolar concentrations of Cur or NC are sufficient for labeling and imaging of Aβ plaques in 5×FAD brain tissue. Cur and NC also labeled different types of Aβ plaques, including core, neuritic, diffuse, and burned-out, to a greater degree than other amyloid-binding dyes. Therefore, Cur and or NC can be used as an alternative to Aβ-specific antibody for labeling and imaging of Aβ plaques ex vivo and in vivo. It can provide an easy and inexpensive means of detecting Aβ-plaque load in postmortem brain tissue of animal models of AD after anti-amyloid therapy.

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Abbreviations

Cur:

Curcumin

NC:

Nanocurcumin

APP:

Amyloid precursor protein

Aβ:

Amyloid beta protein

PET:

Positron emission tomography

AD:

Alzheimer’s disease

Thio-S:

Thioflavin-S

CR:

Congo red

5× FAD:

Five times familiar Alzheimer’s disease

DMSO:

Dimethyl sulfoxide

PBS:

Phosphate buffer saline

ABC:

Avidin biotin complex

DAB:

Diaminobenzidine

PD:

Parkinson’s disease

HD:

Huntington’s disease

AU:

Arbitrary unit

HSD:

Honestly significant difference

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Acknowledgments

Support for this study came from the Field Neurosciences Institute, at St. Mary’s of Michigan. We thank Verdure Science (Noblesville, IN) for donating the nanocurcumin for this study.

Author contributions

P.M. designed, performed the experiments, and collected the data. T.H., N.K., L.P. and C.L. helped with tissue processing. P.M., G.L.D., and J.R. analyzed the data and wrote the manuscript.

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Authors and Affiliations

  1. Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI, 48859, USA

    Panchanan Maiti, Tia C. Hall, Leela Paladugu, Nivya Kolli, Cameron Learman, Julien Rossignol & Gary L. Dunbar

  2. Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI, 48859, USA

    Panchanan Maiti, Tia C. Hall, Leela Paladugu, Nivya Kolli, Cameron Learman, Julien Rossignol & Gary L. Dunbar

  3. Department of Psychology, Central Michigan University, Mt. Pleasant, MI, 48859, USA

    Panchanan Maiti & Gary L. Dunbar

  4. College of Medicine, Central Michigan University, Mt. Pleasant, MI, 48859, USA

    Julien Rossignol

  5. Field Neurosciences Institute, St. Mary’s of Michigan, Saginaw, MI, 48604, USA

    Panchanan Maiti & Gary L. Dunbar

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  1. Panchanan Maiti
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  2. Tia C. Hall
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Correspondence to Panchanan Maiti or Gary L. Dunbar.

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Fig S1

Solubility of Cur and NC in different solvents. A: Large crystals (green fluorescence) were observed in the both Cur powder and solution (100 µM) with all the solvents used, including NaOH (10 N), DMSO, methanol, and PBS, indicating it is less soluble in all these solvents, compared to NC (100 µM), which was solubilized in most of these solvents. Scale bar indicates 250 μm and is applicable to all other images; B: fluorescent intensity of Cur (100 µM) and NC (100 µM) in PBS (0.1 M, pH 7.4) after different time points, indicating dietary Cur was degraded faster than NC. *p < 0.05 and **p < 0.01 compared to 0 hour (AU: arbitrary unit). (PDF 170 kb)

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Maiti, P., Hall, T.C., Paladugu, L. et al. A comparative study of dietary curcumin, nanocurcumin, and other classical amyloid-binding dyes for labeling and imaging of amyloid plaques in brain tissue of 5×-familial Alzheimer’s disease mice. Histochem Cell Biol 146, 609–625 (2016). https://doi.org/10.1007/s00418-016-1464-1

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