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

被引：228

作者：

Betts, Matthew J. ^{[1
,2
]}

Kirilina, Evgeniya ^{[3
,4
]}

Otaduy, Maria C. G. ^{[5
]}

Ivanov, Dimo ^{[6
]}

Acosta-Cabronero, Julio ^{[7
]}

Callaghan, Martina F. ^{[7
]}

Lambert, Christian ^{[7
]}

Cardenas-Blanco, Arturo ^{[1
,2
]}

Pine, Kerrin ^{[3
,7
]}

Passamonti, Luca ^{[8
,9
]}

Loane, Clare ^{[10
]}

Keuken, Max C. ^{[11
,12
]}

Trujillo, Paula ^{[13
]}

Luesebrink, Falk ^{[14
,15
]}

Mattern, Hendrik ^{[14
]}

Liu, Kathy Y. ^{[16
]}

Priovoulos, Nikos ^{[17
]}

Fliessbach, Klaus ^{[18
,19
]}

Dahl, Martin J. ^{[20
]}

Maass, Anne ^{[1
]}

Madelung, Christopher F. ^{[21
]}

Meder, David ^{[21
]}

Ehrenberg, Alexander J. ^{[22
,23
]}

Speck, Oliver ^{[1
,14
,24
,25
]}

Weiskopf, Nikolaus ^{[3
,7
]}

Dolan, Raymond ^{[7
,26
]}

Inglis, Ben ^{[27
]}

Tosun, Duygu ^{[28
]}

Morawski, Markus ^{[29
]}

Zucca, Fabio A. ^{[30
]}

Siebner, Hartwig R. ^{[21
]}

Mather, Mara ^{[31
,32
]}

Uludag, Kamil ^{[33
,34
,35
,36
]}

Heinsen, Helmut ^{[37
,38
]}

Poser, Benedikt A. ^{[6
]}

Howard, Robert ^{[16
]}

Zecca, Luigi ^{[30
,39
]}

Rowe, James B. ^{[8
]}

Grinberg, Lea T. ^{[22
,37
,40
]}

Jacobs, Heidi I. L. ^{[6
,17
,41
]}

Duezel, Emrah ^{[1
,2
,10
]}

Haemmerer, Dorothea ^{[2
,7
,10
]}

机构：

[1] German Ctr Neurodegenerat Dis DZNE, Magdeburg, Germany

[2] Otto von Guericke Univ, Inst Cognit Neurol & Dementia Res, Magdeburg, Germany

[3] Max Planck Inst Human Cognit & Brain Sci, Dept Neurophys, Leipzig, Germany

[4] Free Univ Berlin, Ctr Cognit Neurosci, Berlin, Germany

[5] Univ Sao Paulo, Dept & Inst Radiol, Lab Magnet Resonance LIM44, Med Sch, Sao Paulo, Brazil

[6] Maastricht Univ, Fac Psychol & Neurosci, Dept Cognit Neurosci, NL-6200 MD Maastricht, Netherlands

[7] UCL Inst Neurol, Wellcome Ctr Human Neuroimaging, London, England

[8] Univ Cambridge, Dept Clin Neurosci, Cambridge, England

[9] CNR, IBFM, Milan, Italy

[10] UCL, Inst Cognit Neurosci, London, England

[11] Univ Amsterdam, Integrat Model Based Cognit Neurosci Res Unit, Amsterdam, Netherlands

[12] Leiden Univ, Cognit Psychol, Leiden, Netherlands

[13] Vanderbilt Univ, Med Ctr, Dept Neurol, Nashville, TN USA

[14] Otto von Guericke Univ, Inst Phys, Dept Biomed Magnet Resonance, Magdeburg, Germany

[15] Otto von Guericke Univ, Dept Neurol, Magdeburg, Germany

[16] UCL, Div Psychiat, London, England

[17] Maastricht Univ, Fac Hlth Med & Life Sci, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Maastricht, Netherlands

[18] Univ Hosp Bonn, Dept Neurodegenerat Dis & Geriatr Psychiat, Bonn, Germany

[19] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

[20] Max Planck Inst Human Dev, Ctr Lifespan Psychol, Berlin, Germany

[21] Copenhagen Univ Hosp Hvidovre, Danish Res Ctr Magnet Resonance, Ctr Funct & Diagnost Imaging & Res, Hvidovre, Denmark

[22] Univ Calif San Francisco, Memory & Aging Ctr, Weill Inst Neurosci, San Francisco, CA 94143 USA

[23] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA

[24] Ctr Behav Brain Sci, Magdeburg, Germany

[25] Leibniz Inst Neurobiol, Magdeburg, Germany

[26] UCL, Max Planck Ctr Computat Psychiat & Ageing, London, England

[27] Univ Calif Berkeley, Henry H Wheeler Jr Brain Imaging Ctr, Berkeley, CA 94720 USA

[28] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA

[29] Univ Leipzig, Med Fac, Paul Flechsig Inst Brain Res, Leipzig, Germany

[30] Natl Res Council Italy, Inst Biomed Technol, Milan, Italy

[31] Univ Southern Calif, Leonard Davis Sch Gerontol, Los Angeles, CA USA

[32] Univ Southern Calif, Dept Psychol, Los Angeles, CA USA

[33] Sungkyunkwan Univ, Ctr Neurosci Imaging Res, Inst Basic Sci, Suwon, South Korea

[34] Sungkyunkwan Univ, Dept Biomed Engn, Suwon, South Korea

[35] Univ Hlth Network, Techna Inst, Toronto, ON, Canada

[36] Univ Hlth Network, Koerner Scientist MR Imaging, Toronto, ON, Canada

[37] Univ Sao Paulo, Med Sch, Sao Paulo, Brazil

[38] Univ Wurzburg, Clin Psychiat, Wurzburg, Germany

[39] Columbia Univ, New York State Psychiat Inst, Dept Psychiat, Med Ctr, New York, NY USA

[40] Univ Calif San Francisco, Global Brain Hlth Inst, San Francisco, CA 94143 USA

[41] Harvard Med Sch, Dept Radiol, Div Nucl Med & Mol Imaging, Massachusetts Gen Hosp, Boston, MA 02115 USA

来源：

BRAIN | 2019年 / 142卷

基金：

欧洲研究理事会; 英国惠康基金;

关键词：

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;

D O I：

10.1093/brain/awz193

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：2558 / 2571

页数：14

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