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Lookup NU author(s): Professor Nicola PaveseORCiD, Professor David BrooksORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Noradrenergic neurotransmission may play an important role in tremor modulation through its innervation of key structures of the central tremor circuits. Here, Parkinson's disease (PD) patients with (PDT+) or without (PDT-) rest tremor had 11C-methylreboxetine(11C-MeNER) positron emission tomography (PET) to test the hypothesis that noradrenaline terminal function was relatively preserved in PDT+ compared to PDT-. Methods: Sixty-five PD patients and 28 healthy controls (HC) were scanned with 11C-MeNER PET. Patients were categorized as PDT+ if subscores in UPDRS-III item 3 or MDS-UPDRS-III item 17 was ≥ 2; remaining were categorized as PDT-. Simplified reference tissue model 2 distribution volume ratios (DVR) were calculated for thalamus, dorsal and median raphe, locus coeruleus (LC) and red nucleus using time activity curves (TACs) obtained from volumes of interest (VOI). Data were statistically interrogated with a general linear mixed model using ‘region’, and ‘group’ as factors and the interaction of ‘region x group’ was examined. Results: Tremor positive PD patients had a significantly higher mean 11C-MeNER DVR compared to PDT- in LC and thalamus. The PDT+ mean LC DVR was similar to that of HC. PDT+ mean 11C-MeNER DVRs were significantly lower than HC in the dorsal raphe while the PDT- group showed significantly lower mean 11C-MeNER DVR across all regions compared to HC. Conclusion: While both PD T+ and PD T- groups showed a significant loss of noradrenaline terminal function compared to controls, noradrenergic neurons were relatively preserved in PDT+ in LC and thalamus. The greater loss of noradrenergic transporters in PDT- in LC and thalamus compared with PDT+ is in line with earlier in-vitro studies and could potentially contribute to their tremor negative phenotype.
Author(s): Kinnerup MB, Sommerauer M, Damholdt FM, Schaldemose JL, Ismail R, Terkelsen AJ, Stær K, Hansen A, Fedorova TD, Knudsen K, Skjærbæk C, Borghammer P, Pavese N, Brooks DJ, Nahimi A
Publication type: Article
Publication status: Published
Journal: Neurobiology of Disease
Year: 2021
Volume: 152
Print publication date: 01/05/2021
Online publication date: 05/02/2021
Acceptance date: 03/02/2021
Date deposited: 04/02/2021
ISSN (print): 0969-9961
ISSN (electronic): 1095-953X
Publisher: Academic Press
URL: https://doi.org/10.1016/j.nbd.2021.105295
DOI: 10.1016/j.nbd.2021.105295
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