Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a biomarker for Parkinson’s disease

Abstract

The diagnosis of Parkinson’s disease (PD) occurs after pathogenesis is advanced and many substantia nigra (SN) dopamine neurons have already died. Now that therapies to block this neuronal loss are under development, it is imperative that the disease be diagnosed at earlier stages and that the response to therapies is monitored. Recent studies suggest this can be accomplished by magnetic resonance imaging (MRI) detection of neuromelanin (NM), the characteristic pigment of SN dopaminergic, and locus coeruleus (LC) noradrenergic neurons. NM is an autophagic product synthesized via oxidation of catecholamines and subsequent reactions, and in the SN and LC it increases linearly during normal aging. In PD, however, the pigment is lost when SN and LC neurons die. As shown nearly 25 years ago by Zecca and colleagues, NM’s avid binding of iron provides a paramagnetic source to enable electron and nuclear magnetic resonance detection, and thus a means for safe and noninvasive measure in living human brain. Recent technical improvements now provide a means for MRI to differentiate between PD patients and age-matched healthy controls, and should be able to identify changes in SN NM with age in individuals. We discuss how MRI detects NM and how this approach might be improved. We suggest that MRI of NM can be used to confirm PD diagnosis and monitor disease progression. We recommend that for subjects at risk for PD, and perhaps generally for older people, that MRI sequences performed at regular intervals can provide a pre-clinical means to detect presymptomatic PD.

Contributors

David Sulzer: [e-mail]

Luigi Zecca: [e-mail]

Journal

Journal ID (nlm-ta): NPJ Parkinsons Dis

Journal ID (iso-abbrev): NPJ Parkinsons Dis

Title: NPJ Parkinson's Disease

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2373-8057

Publication date (Electronic): 10 April 2018

Publication date PMC-release: 10 April 2018

Publication date Collection: 2018

Volume: 4

Affiliations

[1 ]ISNI 0000 0000 8499 1112, GRID grid.413734.6, Department of Psychiatry, Columbia University Medical Center , , New York State Psychiatric Institute, ; New York, NY USA

[2 ]ISNI 0000 0001 2285 2675, GRID grid.239585.0, Department of Neurology, , Columbia University Medical Center, ; New York, NY USA

[3 ]ISNI 0000 0001 2285 2675, GRID grid.239585.0, Department of Pharmacology, , Columbia University Medical Center, ; New York, NY USA

[4 ]ISNI 0000 0001 2182 2255, GRID grid.28046.38, The Royal’s Institute of Mental Health Research, , Affiliated with the University of Ottawa, ; Ottawa, ON Canada

[5 ]ISNI 0000 0004 1762 5736, GRID grid.8982.b, Department of Chemistry, , University of Pavia, ; Pavia, Italy

[6 ]Parkinson Institute, ASST “Gaetano Pini-CTO”, Milan, Italy

[7 ]ISNI 0000 0001 2222 1582, GRID grid.266097.c, Center for Advanced NeuroImaging, , University of California Riverside, ; Riverside, CA USA

[8 ]ISNI 0000 0001 2222 1582, GRID grid.266097.c, Department of Bioengineering, , University of California Riverside, ; Riverside, CA USA

[9 ]ISNI 0000 0001 1940 4177, GRID grid.5326.2, Institute of Biomedical Technologies, , National Research Council of Italy, ; Milan, Italy

[10 ]Department of Neurology, University Hospital and Julius-Maximillian-University, Wuerzburg, Germany

Article

Publisher ID: 47

DOI: 10.1038/s41531-018-0047-3

PMC ID: 5893576

Copyright statement: © The Author(s) 2018

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Categories

Subject: Review Article

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issue-copyright-statement © The Author(s) 2018