000163310 001__ 163310
000163310 005__ 20240305153450.0
000163310 0247_ $$2doi$$a10.1093/brain/awab236
000163310 0247_ $$2pmid$$apmid:34196700
000163310 0247_ $$2ISSN$$a0006-8950
000163310 0247_ $$2ISSN$$a1460-2156
000163310 0247_ $$2altmetric$$aaltmetric:108531568
000163310 037__ $$aDZNE-2022-00090
000163310 041__ $$aEnglish
000163310 082__ $$a610
000163310 1001_ $$00000-0002-1341-0389$$aDoppler, Christopher E J$$b0
000163310 245__ $$aRegional locus coeruleus degeneration is uncoupled from noradrenergic terminal loss in Parkinson's disease.
000163310 260__ $$aOxford$$bOxford Univ. Press$$c2021
000163310 3367_ $$2DRIVER$$aarticle
000163310 3367_ $$2DataCite$$aOutput Types/Journal article
000163310 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1709649269_29109
000163310 3367_ $$2BibTeX$$aARTICLE
000163310 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000163310 3367_ $$00$$2EndNote$$aJournal Article
000163310 520__ $$aPrevious studies have reported substantial involvement of the noradrenergic system in Parkinson's disease. 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. Combining these methods, we investigated the relationship of neurodegeneration in these distinct compartments in Parkinson's disease. We examined 93 subjects (40 healthy controls and 53 Parkinson's 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. 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's disease showed reduced locus coeruleus MRI contrast independently of the selected method (voxel approaches: P < 0.0001, P < 0.001; probabilistic map: P < 0.05), specifically on the clinically-defined most affected side (P < 0.05), and reduced locus coeruleus volume (P < 0.0001). Reduced MRI contrast was confined to the middle and caudal locus coeruleus (voxel approach, rostral: P = 0.48, middle: P < 0.0001, and caudal: P < 0.05; probabilistic map, rostral: P = 0.90, middle: P < 0.01, and caudal: P < 0.05). The noradrenaline transporter density was lower in patients with Parkinson's diseasein all examined regions (group effect P < 0.0001). 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's disease patients in all examined regions (group effect P < 0.001). Our multimodal imaging approach revealed pronounced noradrenergic terminal loss relative to cellular locus coeruleus degeneration in Parkinson's disease; the latter followed a distinct spatial pattern with the middle-caudal portion being more affected than the rostral part. The data shed first light on the interaction between the axonal and cell body compartments and their differential susceptibility to neurodegeneration in Parkinson's disease, which may eventually direct research towards potential novel treatment approaches.
000163310 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0
000163310 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000163310 650_7 $$2Other$$aMeNER
000163310 650_7 $$2Other$$aParkinson’s disease
000163310 650_7 $$2Other$$aneuromelanin
000163310 650_7 $$2Other$$anoradrenaline
000163310 650_7 $$2Other$$apositron emission tomography
000163310 650_7 $$2NLM Chemicals$$aNorepinephrine Plasma Membrane Transport Proteins
000163310 650_7 $$2NLM Chemicals$$aSLC6A2 protein, human
000163310 650_2 $$2MeSH$$aAged
000163310 650_2 $$2MeSH$$aAged, 80 and over
000163310 650_2 $$2MeSH$$aFemale
000163310 650_2 $$2MeSH$$aHumans
000163310 650_2 $$2MeSH$$aLocus Coeruleus: diagnostic imaging
000163310 650_2 $$2MeSH$$aLocus Coeruleus: metabolism
000163310 650_2 $$2MeSH$$aMagnetic Resonance Imaging: methods
000163310 650_2 $$2MeSH$$aMale
000163310 650_2 $$2MeSH$$aMiddle Aged
000163310 650_2 $$2MeSH$$aMultimodal Imaging: methods
000163310 650_2 $$2MeSH$$aNorepinephrine Plasma Membrane Transport Proteins: metabolism
000163310 650_2 $$2MeSH$$aParkinson Disease: diagnostic imaging
000163310 650_2 $$2MeSH$$aParkinson Disease: metabolism
000163310 650_2 $$2MeSH$$aPositron-Emission Tomography: methods
000163310 7001_ $$aKinnerup, Martin B$$b1
000163310 7001_ $$aBrune, Corinna$$b2
000163310 7001_ $$aFarrher, Ezequiel$$b3
000163310 7001_ $$0P:(DE-2719)2810555$$aBetts, Matthew$$b4$$udzne
000163310 7001_ $$aFedorova, Tatyana D$$b5
000163310 7001_ $$aSchaldemose, Jeppe L$$b6
000163310 7001_ $$aKnudsen, Karoline$$b7
000163310 7001_ $$aIsmail, Rola$$b8
000163310 7001_ $$aSeger, Aline D$$b9
000163310 7001_ $$aHansen, Allan K$$b10
000163310 7001_ $$aStær, Kristian$$b11
000163310 7001_ $$aFink, Gereon R$$b12
000163310 7001_ $$00000-0003-2602-2518$$aBrooks, David J$$b13
000163310 7001_ $$aNahimi, Adjmal$$b14
000163310 7001_ $$00000-0001-6391-8052$$aBorghammer, Per$$b15
000163310 7001_ $$00000-0001-5723-9766$$aSommerauer, Michael$$b16
000163310 773__ $$0PERI:(DE-600)1474117-9$$a10.1093/brain/awab236$$gVol. 144, no. 9, p. 2732 - 2744$$n9$$p2732 - 2744$$tBrain$$v144$$x1460-2156$$y2021
000163310 909CO $$ooai:pub.dzne.de:163310$$pVDB
000163310 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810555$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b4$$kDZNE
000163310 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0
000163310 9141_ $$y2021
000163310 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-01-29
000163310 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-01-29
000163310 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-01-29
000163310 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2022-11-09$$wger
000163310 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-09
000163310 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-09
000163310 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-09
000163310 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-09
000163310 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-09
000163310 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2022-11-09
000163310 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-09
000163310 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBRAIN : 2021$$d2022-11-09
000163310 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2022-11-09
000163310 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2022-11-09
000163310 915__ $$0StatID:(DE-HGF)9915$$2StatID$$aIF >= 15$$bBRAIN : 2021$$d2022-11-09
000163310 9201_ $$0I:(DE-2719)5000006$$kAG Düzel$$lClinical Neurophysiology and Memory$$x0
000163310 980__ $$ajournal
000163310 980__ $$aVDB
000163310 980__ $$aI:(DE-2719)5000006
000163310 980__ $$aUNRESTRICTED