Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases

Matthew J Betts, Evgeniya Kirilina, Maria C G Otaduy, Dimo Ivanov, Julio Acosta-Cabronero, Martina F Callaghan, Christian Lambert, Arturo Cardenas-Blanco, Kerrin Pine, Luca Passamonti, Clare Loane, Max C Keuken, Paula Trujillo, Falk Lüsebrink, Hendrik Mattern, Kathy Y Liu, Nikos Priovoulos, Klaus Fliessbach, Martin J Dahl, Anne MaaßChristopher F Madelung, David Meder, Alexander J Ehrenberg, Oliver Speck, Nikolaus Weiskopf, Raymond Dolan, Ben Inglis, Duygu Tosun, Markus Morawski, Fabio A Zucca, Hartwig R Siebner, Mara Mather, Kamil Uludag, Helmut Heinsen, Benedikt A Poser, Robert Howard, Luigi Zecca, James B Rowe, Lea T Grinberg, Heidi I L Jacobs, Emrah Düzel, Dorothea Hämmerer

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer's disease, atypical neurodegenerative dementias and Parkinson's disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.

Original languageEnglish
Pages (from-to)2558–2571
Number of pages14
JournalBrain
Volume142
Issue number9
Early online date20 Jul 2019
DOIs
Publication statusPublished - Sep 2019

Keywords

  • locus coeruleus (LC)
  • magnetic resonance imaging (MRI)
  • neurodegeneration
  • noradrenaline (NA)
  • biomarker
  • MULTIPLE SYSTEM ATROPHY
  • HUMAN SUBSTANTIA-NIGRA
  • IN-VIVO VISUALIZATION
  • PARKINSONS-DISEASE
  • ALZHEIMERS-DISEASE
  • COGNITIVE RESERVE
  • RELAXATION-TIMES
  • NERVOUS-SYSTEM
  • HUMAN BRAIN
  • NEUROMELANIN

Cite this

Betts, M. J., Kirilina, E., Otaduy, M. C. G., Ivanov, D., Acosta-Cabronero, J., Callaghan, M. F., Lambert, C., Cardenas-Blanco, A., Pine, K., Passamonti, L., Loane, C., Keuken, M. C., Trujillo, P., Lüsebrink, F., Mattern, H., Liu, K. Y., Priovoulos, N., Fliessbach, K., Dahl, M. J., ... Hämmerer, D. (2019). Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases. Brain, 142(9), 2558–2571. https://doi.org/10.1093/brain/awz193