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Neuromelanin-sensitive MRI sequences and PET tracers have become available to visualize the cell bodies in the locus coeruleus and the density of noradrenergic terminal transporters.<\/jats:p>\n                  <jats:p>Combining these methods, we investigated the relationship of neurodegeneration in these distinct compartments in Parkinson\u2019s disease. We examined 93 subjects (40 healthy controls and 53 Parkinson\u2019s disease patients) with neuromelanin-sensitive turbo spin-echo MRI and calculated locus coeruleus-to-pons signal contrasts. Voxels with the highest intensities were extracted from published locus coeruleus coordinates transformed to individual MRI. To also investigate a potential spatial pattern of locus coeruleus degeneration, we extracted the highest signal intensities from the rostral, middle, and caudal third of the locus coeruleus. Additionally, a study-specific probabilistic map of the locus coeruleus was created and used to extract mean MRI contrast from the entire locus coeruleus and each rostro-caudal subdivision. Locus coeruleus volumes were measured using manual segmentations.<\/jats:p>\n                  <jats:p>A subset of 73 subjects had 11C-MeNER PET to determine noradrenaline transporter density, and distribution volume ratios of noradrenaline transporter-rich regions were computed. Patients with Parkinson\u2019s disease showed reduced locus coeruleus MRI contrast independently of the selected method (voxel approaches: P\u2009&amp;lt;\u20090.0001, P\u2009&amp;lt;\u20090.001; probabilistic map: P\u2009&amp;lt;\u20090.05), specifically on the clinically-defined most affected side (P\u2009&amp;lt;\u20090.05), and reduced locus coeruleus volume (P\u2009&amp;lt;\u20090.0001). Reduced MRI contrast was confined to the middle and caudal locus coeruleus (voxel approach, rostral: P\u2009=\u20090.48, middle: P\u2009&amp;lt;\u20090.0001, and caudal: P\u2009&amp;lt;\u20090.05; probabilistic map, rostral: P\u2009=\u20090.90, middle: P\u2009&amp;lt;\u20090.01, and caudal: P\u2009&amp;lt;\u20090.05). The noradrenaline transporter density was lower in patients with Parkinson\u2019s diseasein all examined regions (group effect P\u2009&amp;lt;\u20090.0001). No significant correlation was observed between locus coeruleus MRI contrast and noradrenaline transporter density. In contrast, the individual ratios of noradrenaline transporter density and locus coeruleus MRI contrast were lower in Parkinson\u2019s disease patients in all examined regions (group effect P\u2009&amp;lt;\u20090.001). Our multimodal imaging approach revealed pronounced noradrenergic terminal loss relative to cellular locus coeruleus degeneration in Parkinson\u2019s disease; the latter followed a distinct spatial pattern with the middle-caudal portion being more affected than the rostral part.<\/jats:p>\n                  <jats:p>The data shed first light on the interaction between the axonal and cell body compartments and their differential susceptibility to neurodegeneration in Parkinson\u2019s disease, which may eventually direct research towards potential novel treatment approaches.<\/jats:p>","DOI":"10.1093\/brain\/awab236","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T15:18:34Z","timestamp":1624893514000},"page":"2732-2744","source":"Crossref","is-referenced-by-count":104,"title":["Regional locus coeruleus degeneration is uncoupled from noradrenergic terminal loss in Parkinson\u2019s disease"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1341-0389","authenticated-orcid":false,"given":"Christopher E J","family":"Doppler","sequence":"first","affiliation":[{"name":"Institute of Neuroscience and Medicine (INM-3), Forschungszentrum J\u00fclich, D-52425 J\u00fclich, Germany"},{"name":"Faculty of Medicine and University Hospital Cologne, Department of Neurology, University of Cologne, D-50937 K\u00f6ln, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin B","family":"Kinnerup","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital, DK-8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Brune","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Department of Neurology, University of Cologne, D-50937 K\u00f6ln, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezequiel","family":"Farrher","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine (INM-4), Forschungszentrum J\u00fclich, D-52425 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Betts","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), D-39120 Magdeburg, Germany"},{"name":"Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University Magdeburg, D-39120 Magdeburg, Germany"},{"name":"Center for Behavioral Brain Sciences, University of Magdeburg, D-39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana D","family":"Fedorova","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital, DK-8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeppe L","family":"Schaldemose","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital, DK-8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karoline","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital, DK-8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rola","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital, DK-8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline D","family":"Seger","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine (INM-3), Forschungszentrum J\u00fclich, D-52425 J\u00fclich, Germany"},{"name":"Faculty of Medicine and University Hospital Cologne, Department of Neurology, University of Cologne, D-50937 K\u00f6ln, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan K","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital, DK-8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"St\u00e6r","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital, DK-8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gereon R","family":"Fink","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine (INM-3), Forschungszentrum J\u00fclich, D-52425 J\u00fclich, Germany"},{"name":"Faculty of Medicine and University Hospital Cologne, Department of Neurology, University of Cologne, D-50937 K\u00f6ln, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2602-2518","authenticated-orcid":false,"given":"David J","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital, DK-8200 Aarhus N, Denmark"},{"name":"Division of Brain Sciences, Imperial College London, London SW7 2AZ, UK"},{"name":"Institute of Translational and Clinical Research, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 7RU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adjmal","family":"Nahimi","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital, DK-8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6391-8052","authenticated-orcid":false,"given":"Per","family":"Borghammer","sequence":"additional","affiliation":[{"name":"Department of 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