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Histochemistry and Cell Biology

, Volume 146, Issue 5, pp 609–625 | Cite as

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

  • Panchanan Maiti
  • Tia C. Hall
  • Leela Paladugu
  • Nivya Kolli
  • Cameron Learman
  • Julien Rossignol
  • Gary L. Dunbar
Original Paper

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.

Keywords

Curcumin Nanocurcumin Protein labelling Alzheimer's disease Amyloid beta protein 

Abbreviations

Cur

Curcumin

NC

Nanocurcumin

APP

Amyloid precursor protein

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

Notes

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.

Compliance with ethical standards

Conflict of interest

Authors declare that there is no conflict of interest to publish this research article.

Supplementary material

418_2016_1464_MOESM1_ESM.pdf (170 kb)
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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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Panchanan Maiti
    • 1
    • 2
    • 3
    • 5
  • Tia C. Hall
    • 1
    • 2
  • Leela Paladugu
    • 1
    • 2
  • Nivya Kolli
    • 1
    • 2
  • Cameron Learman
    • 1
    • 2
  • Julien Rossignol
    • 1
    • 2
    • 4
  • Gary L. Dunbar
    • 1
    • 2
    • 3
    • 5
  1. 1.Field Neurosciences Institute Laboratory for Restorative NeurologyCentral Michigan UniversityMt. PleasantUSA
  2. 2.Program in NeuroscienceCentral Michigan UniversityMt. PleasantUSA
  3. 3.Department of PsychologyCentral Michigan UniversityMt. PleasantUSA
  4. 4.College of MedicineCentral Michigan UniversityMt. PleasantUSA
  5. 5.Field Neurosciences InstituteSt. Mary’s of MichiganSaginawUSA

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