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Ultraviolet–visible–near-infrared optical properties of amyloid fibrils shed light on amyloidogenesis

Abstract

Amyloid fibres attract considerable interest due to their biological role in neurodegenerative diseases and their potential as functional biomaterials. Here, we describe an intrinsic signal of amyloid fibres in the near-infrared range. When combined with their recently reported blue luminescence, it paves the way towards new blueprints for the label-free detection of amyloid deposits in in vitro and in vivo contexts. The blue luminescence allows for staining-free characterization of amyloid deposits in human samples. The near-infrared signal offers promising prospects for innovative diagnostic strategies for neurodegenerative diseases—to improve medical care and for the development of new therapies. As a proof of concept, we demonstrate direct detection of amyloid deposits within brains of living, aged mice with Alzheimer’s disease using non-invasive and contrast-agent-free imaging. Ultraviolet–visible–near-infrared optical properties of amyloids open new research avenues for amyloidosis as well as for next-generation biophotonic devices.

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The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by Euronanomed ENMII JTC2012 (project 2011-ERA-002-01- Dia-Amyl) and the French National Research Agency (ANR) through the grants ANR-12-RPIB Multimage and ANR-17-CE09-0013 Bionics (ANR-17-CE09-0013-01 and ANR-17-CE09-0013-02). J.P. is grateful to the Fondation pour la Recherche Médicale (FRM) for granting his PhD fellowship (grant number FRM DBS2013112844<0). A.R. and S.-J.L. acknowledge Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA) for the funding of their respective CEA-Phare PhD fellowships. We thank M. Dumoulin for the gift of α-synuclein, and S. Denti and S. Chierici for the gift of hTau used in this work. This research benefited from resources of the European Synchrotron Radiation Facility (ESRF, Grenoble, France). In particular, we acknowledge M. Burghammer, M. Sztucki and T.G. Dane of the Microfocus beamline ID13. We thank D. Fenel, C. Moriscot and G. Schoehn from the Electron Microscopy platform of the Integrated Structural Biology of Grenoble (ISBG, UMI3265). We thank L. Gonon and V. Mareau for helpful discussions on Raman scattering. We are grateful to L. Kurzawa (µLife platform of CEA-Grenoble/BIG) for helpful discussions and specific advice on confocal microscopy. Fluorescence imaging systems used in this study were acquired thanks to France Life Imaging (French program “Investissement d’Avenir” grant; “Infrastructure d’avenir en Biologie Sante”, ANR-11-INBS-44 0006). This work was also supported by NeuroCoG IDEX UGA in the framework of the “Investissements d’avenir” programme (ANR-15-IDEX-02).

Author information

J.P. and V.F. conceived and designed the work, and wrote most of the paper. J.P., S-J.L., D.I., O.C.-P. and C.V. performed the in vitro characterizations of the amyloid fibres. A.R., T.D. and P.R. conceived, performed and analysed the X-ray scattering experiments. M.M.S. and E.K. collected and prepared the human samples. J.P. and C.M. designed and performed the ex vivo experiments. V.J., M.G., J.V., A.F., Y.U. and J.L.C. performed the 3D and 2D fluorescence imaging and analysed the data. J.P., C.M. and V.F. coordinated all experiments and compiled the results. J.P., C.M., P.R. and V.F. edited the text. All co-authors discussed and commented on the manuscript.

Competing interests

The authors declare no competing interests.

Correspondence to Vincent Forge.

Supplementary information

  1. Supplementary Information

    This file contains more information about the work and Supplementary Figures 1–14.

  2. Reporting Summary

  3. Supplementary Video 1

    Video made with 60 ex vivo confocal microscopy images of isolated amyloid plaque in brain tissue from a patient with Alzheimer’s disease within the hippocampus area.

  4. Supplementary Video 2

    Video made with 60 ex vivo confocal microscopy images of amyloid deposits near a blood vessel in brain tissue from a patient with Alzheimer’s disease within the hippocampus area.

  5. Supplementary Video 3

    Sequential 3D modelling using ex vivo confocal microscopy images of isolated amyloid plaque in brain tissue from a patient with Alzheimer’s disease within the hippocampus area.

  6. Supplementary Video 4

    Sequential 3D modelling using ex vivo confocal microscopy images of amyloid deposits near a blood vessel in brain tissue from a patient with Alzheimer’s disease within the hippocampus area.

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About this article

Fig. 1: UV–vis–NIR luminescence of Het-s prion domain and Aβ1–42 amyloid fibres.
Fig. 2: Luminescence properties of insulin amyloid protein during fibre growth process.
Fig. 3: Ex vivo confocal microscopy images of amyloid deposits in brain slices from pateints with Alzheimer’s disease within the hippocampus area.
Fig. 4: Detection of amyloid deposits by 3D NIR imaging in mice with Alzheimer’s disease and control mice.
Fig. 5: Non-invasive detection of amyloid deposits by 2D NIR imaging using Fluobeam800.