VMAT2 availability in Parkinson’s disease with probable REM sleep behaviour disorder

Abstract REM sleep behaviour disorder (RBD) can be an early non-motor symptom of Parkinson’s disease (PD) with pathology involving mainly the pontine nuclei. Beyond the brainstem, it is unclear if RBD patients comorbid with PD have more affected striatal dopamine denervation compared to PD patients...

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Autores principales:	Mikaeel Valli, Sang Soo Cho, Carme Uribe, Mario Masellis, Robert Chen, Alexander Mihaescu, Antonio P. Strafella
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Parkinson’s disease REM sleep behaviour disorder Positron emission tomography VMAT2 [11C]DTBZ Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/5dcd41733e1541eab8faeaa61f6f7af3
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spelling	oai:doaj.org-article:5dcd41733e1541eab8faeaa61f6f7af32021-11-14T12:42:37ZVMAT2 availability in Parkinson’s disease with probable REM sleep behaviour disorder10.1186/s13041-021-00875-71756-6606https://doaj.org/article/5dcd41733e1541eab8faeaa61f6f7af32021-11-01T00:00:00Zhttps://doi.org/10.1186/s13041-021-00875-7https://doaj.org/toc/1756-6606Abstract REM sleep behaviour disorder (RBD) can be an early non-motor symptom of Parkinson’s disease (PD) with pathology involving mainly the pontine nuclei. Beyond the brainstem, it is unclear if RBD patients comorbid with PD have more affected striatal dopamine denervation compared to PD patients unaffected by RBD (PD-RBD−). To elucidate this, we evaluated the availability of vesicular monoamine transporter 2 (VMAT2), an index of nigrostriatal dopamine innervation, in 15 PD patients with probable RBD (PD-RBD+), 15 PD-RBD−, and 15 age-matched healthy controls (HC) using [11C]DTBZ PET imaging. This technique measured VMAT2 availability within striatal regions of interest (ROI). A mixed effect model was used to compare the radioligand binding of VMAT2 between the three groups for each striatal ROI, while co-varying for sex, cognitive function and depression scores. Multiple regressions were also computed to predict clinical measures from group condition and VMAT2 binding within all ROIs explored. We observed a significant main effect of group condition on VMAT2 availability within the caudate, putamen, ventral striatum, globus pallidus, substantia nigra, and subthalamus. Specifically, our results revealed that PD-RBD+ had lower VMAT2 availability compared to HC in all these regions except for the subthalamus and substantia nigra, while PD-RBD− was significantly lower than HC in all these regions. PD-RBD− showed a negative relationship between motor severity and VMAT2 availability within the left caudate. Our findings reflect that both PD patient subgroups had similar denervation within the nigrostriatal pathway. There were no significant interactions detected between radioligand binding and clinical scores in PD-RBD+. Taken together, VMAT2 and striatal dopamine denervation in general may not be a significant contributor to the pathophysiology of RBD in PD patients. Future studies are encouraged to explore other underlying neural chemistry mechanisms contributing to RBD in PD patients.Mikaeel ValliSang Soo ChoCarme UribeMario MasellisRobert ChenAlexander MihaescuAntonio P. StrafellaBMCarticleParkinson’s diseaseREM sleep behaviour disorderPositron emission tomographyVMAT2[11C]DTBZNeurology. Diseases of the nervous systemRC346-429ENMolecular Brain, Vol 14, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Parkinson’s disease REM sleep behaviour disorder Positron emission tomography VMAT2 [11C]DTBZ Neurology. Diseases of the nervous system RC346-429
spellingShingle	Parkinson’s disease REM sleep behaviour disorder Positron emission tomography VMAT2 [11C]DTBZ Neurology. Diseases of the nervous system RC346-429 Mikaeel Valli Sang Soo Cho Carme Uribe Mario Masellis Robert Chen Alexander Mihaescu Antonio P. Strafella VMAT2 availability in Parkinson’s disease with probable REM sleep behaviour disorder
description	Abstract REM sleep behaviour disorder (RBD) can be an early non-motor symptom of Parkinson’s disease (PD) with pathology involving mainly the pontine nuclei. Beyond the brainstem, it is unclear if RBD patients comorbid with PD have more affected striatal dopamine denervation compared to PD patients unaffected by RBD (PD-RBD−). To elucidate this, we evaluated the availability of vesicular monoamine transporter 2 (VMAT2), an index of nigrostriatal dopamine innervation, in 15 PD patients with probable RBD (PD-RBD+), 15 PD-RBD−, and 15 age-matched healthy controls (HC) using [11C]DTBZ PET imaging. This technique measured VMAT2 availability within striatal regions of interest (ROI). A mixed effect model was used to compare the radioligand binding of VMAT2 between the three groups for each striatal ROI, while co-varying for sex, cognitive function and depression scores. Multiple regressions were also computed to predict clinical measures from group condition and VMAT2 binding within all ROIs explored. We observed a significant main effect of group condition on VMAT2 availability within the caudate, putamen, ventral striatum, globus pallidus, substantia nigra, and subthalamus. Specifically, our results revealed that PD-RBD+ had lower VMAT2 availability compared to HC in all these regions except for the subthalamus and substantia nigra, while PD-RBD− was significantly lower than HC in all these regions. PD-RBD− showed a negative relationship between motor severity and VMAT2 availability within the left caudate. Our findings reflect that both PD patient subgroups had similar denervation within the nigrostriatal pathway. There were no significant interactions detected between radioligand binding and clinical scores in PD-RBD+. Taken together, VMAT2 and striatal dopamine denervation in general may not be a significant contributor to the pathophysiology of RBD in PD patients. Future studies are encouraged to explore other underlying neural chemistry mechanisms contributing to RBD in PD patients.
format	article
author	Mikaeel Valli Sang Soo Cho Carme Uribe Mario Masellis Robert Chen Alexander Mihaescu Antonio P. Strafella
author_facet	Mikaeel Valli Sang Soo Cho Carme Uribe Mario Masellis Robert Chen Alexander Mihaescu Antonio P. Strafella
author_sort	Mikaeel Valli
title	VMAT2 availability in Parkinson’s disease with probable REM sleep behaviour disorder
title_short	VMAT2 availability in Parkinson’s disease with probable REM sleep behaviour disorder
title_full	VMAT2 availability in Parkinson’s disease with probable REM sleep behaviour disorder
title_fullStr	VMAT2 availability in Parkinson’s disease with probable REM sleep behaviour disorder
title_full_unstemmed	VMAT2 availability in Parkinson’s disease with probable REM sleep behaviour disorder
title_sort	vmat2 availability in parkinson’s disease with probable rem sleep behaviour disorder
publisher	BMC
publishDate	2021
url	https://doaj.org/article/5dcd41733e1541eab8faeaa61f6f7af3
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_version_	1718429050390708224

VMAT2 availability in Parkinson’s disease with probable REM sleep behaviour disorder

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