GBA variants in Parkinson’s disease: clinical, metabolomic and multimodal neuroimaging phenotypes

Greuel, Andrea; Trezzi, Jean-Pierre; Glaab, Enrico; Ruppert, Marina C.; Maier, Franziska; Jäger, Christian; Hodak, Zdenka; Lohmann, Katja; Yilong, Ma; Eidelberg, David; Timmermann, Lars; Hiller, Karsten; Tittgemeyer, Marc; Drzezga, Alexander; Diederich, Nico; Eggers, Carsten

doi:10.1002/mds.28225

Reference : GBA variants in Parkinson’s disease: clinical, metabolomic and multimodal neuroimagin...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biotechnology Life sciences : Multidisciplinary, general & others Human health sciences : Neurology
	Focus Areas :	Systems Biomedicine
	To cite this reference:	http://hdl.handle.net/10993/43780

Title :	GBA variants in Parkinson’s disease: clinical, metabolomic and multimodal neuroimaging phenotypes
Language :	English
Author, co-author :	Greuel, Andrea []
	Trezzi, Jean-Pierre [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Glaab, Enrico [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Ruppert, Marina C. []
	Maier, Franziska []
	Jäger, Christian [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Hodak, Zdenka []
	Lohmann, Katja []
	Yilong, Ma []
	Eidelberg, David []
	Timmermann, Lars []
	Hiller, Karsten []
	Tittgemeyer, Marc []
	Drzezga, Alexander []
	Diederich, Nico []
	Eggers, Carsten []
Publication date :	2020
Journal title :	Movement Disorders
Publisher :	John Wiley & Sons
Volume :	35
Issue/season :	12
Pages :	2201-2210
Peer reviewed :	Yes (verified by ORBi^lu)
Audience :	International
ISSN :	0885-3185
e-ISSN :	1531-8257
City :	Hoboken
Country :	NY
Keywords :	[en] GBA ; Parkinson's disease ; genetics ; metabolomics ; neuroimaging ; multimodal ; functional ; statistics
Abstract :	[en] Background: Alterations in the GBA gene (NM_000157.3) are the most important genetic risk factor for Parkinson’s disease. Biallelic GBA mutations cause the lysosomal storage disorder Gaucher´s disease. The GBA variants p.E365K and p.T408M are associated with Parkinson’s but not with Gaucher´s disease. The pathophysiological role of these variants needs to be further explored. Objective: This study analyzed the clinical, neuropsychological, metabolic and neuroimaging phenotypes of Parkinson’s disease patients carrying the GBA variants p.E365K and p.T408M. Methods: GBA was sequenced in 56 mid-stage Parkinson’s disease patients. Carriers of GBA variants were compared to non-carriers regarding clinical history and symptoms, neuropsychological features, metabolomics and multimodal neuroimaging. Blood plasma gas chromatography coupled to mass spectrometry, [18F]FDopa PET, [18F]FDG PET, and resting-state fMRI were performed. Results: Sequence analysis detected 13 heterozygous GBA variant carriers (seven with p.E365K, six with p.T408M). One patient carried a GBA mutation (p.N409S) and was excluded. Clinical history and symptoms were not significantly different between groups. Global cognitive performance was lower in variant carriers. Metabolomic group differences were suggestive of more severe Parkinson’s disease-related alterations in carriers versus non-carriers. [18F]FDopa and [18F]FDG PET showed signs of a more advanced disease; [18F]FDG PET and fMRI showed similarities with Lewy body dementia and Parkinson’s disease dementia in carriers. Conclusions: This is the first study to comprehensively assess (neuro-)biological phenotypes of GBA variants in Parkinson’s disease. Metabolomics and neuroimaging detected more significant group differences than clinical and behavioral evaluation. These alterations could be promising to monitor effects of disease-modifying treatments targeting glucocerebrosidase metabolism.
Research centres :	Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
Funders :	Fonds National de la Recherche - FnR
Name of the research project :	FNR11651464 > PD-Strat > Multi-dimensional stratification of Parkinson’s disease patients for personalised interventions > 01/07/2018 > 30/06/2021 > 2018 GLAAB Enrico
Target :	Researchers ; Professionals ; Students
Permalink :	http://hdl.handle.net/10993/43780
DOI :	10.1002/mds.28225
Other URL :	http://dx.doi.org/10.1002/mds.28225
Mentions required by the publisher for OA :	The original publication is available at http://dx.doi.org/10.1002/mds.28225
FnR project :	FnR ; FNR11651464 > Enrico Glaab > PD-Strat > Multi-dimensional stratification of Parkinson’s disease patients for personalised interventions > 01/07/2018 > 30/06/2021 > 2018

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