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


Type
Article
Change log
Authors
Betts, Matthew J 
Kirilina, Evgeniya 
Otaduy, Maria CG 
Ivanov, Dimo 
Acosta-Cabronero, Julio 
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.

Description
Keywords
locus coeruleus (LC), magnetic resonance imaging (MRI), neurodegeneration, noradrenaline (NA), biomarker
Journal Title
Brain
Conference Name
Journal ISSN
0006-8950
1460-2156
Volume Title
142
Publisher
Oxford University Press
Sponsorship
Wellcome Trust (103838/Z/14/Z)
Medical Research Council (MR/P01271X/1)
Includes MRC, NIHR, Wellcome Trust, H2020 and FP7.