% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Greuel:154385,
author = {Greuel, Andrea and Trezzi, Jean-Pierre and Glaab, Enrico
and Ruppert, Marina C and Maier, Franziska and Jäger,
Christian and Hodak, Zdenka and Lohmann, Katja and Ma,
Yilong and Eidelberg, David and Timmermann, Lars and Hiller,
Karsten and Tittgemeyer, Marc and Drzezga, Alexander and
Diederich, Nico and Eggers, Carsten},
title = {{GBA} {V}ariants in {P}arkinson's {D}isease: {C}linical,
{M}etabolomic, and {M}ultimodal {N}euroimaging
{P}henotypes.},
journal = {Movement disorders},
volume = {35},
number = {12},
issn = {1531-8257},
address = {New York, NY},
publisher = {Wiley},
reportid = {DZNE-2021-00238},
pages = {2201 - 2210},
year = {2020},
note = {ISSN 1531-8257 not unique: **3 hits**.},
abstract = {Alterations in the GBA gene $(NM_000157.3)$ are the most
important genetic risk factor for Parkinson's disease (PD).
Biallelic GBA mutations cause the lysosomal storage disorder
Gaucher's disease. The GBA variants p.E365K and p.T408M are
associated with PD but not with Gaucher's disease. The
pathophysiological role of these variants needs to be
further explored.This study analyzed clinical,
neuropsychological, metabolic, and neuroimaging phenotypes
of patients with PD carrying the GBA variants p.E365K and
p.T408M.GBA was sequenced in 56 patients with mid-stage PD.
Carriers of GBA variants were compared with noncarriers
regarding clinical history and symptoms, neuropsychological
features, metabolomics, and multimodal neuroimaging. Blood
plasma gas chromatography coupled to mass spectrometry,
6-[18 F]fluoro-L-Dopa positron emission tomography (PET),
[18 F]fluorodeoxyglucose PET, and resting-state functional
magnetic resonance imaging were performed.Sequence analysis
detected 13 heterozygous GBA variant carriers (7 with
p.E365K, 6 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
PD-related alterations in carriers versus noncarriers. Both
PET scans showed signs of a more advanced disease; [18
F]fluorodeoxyglucose PET and functional magnetic resonance
imaging showed similarities with Lewy body dementia and PD
dementia in carriers.This is the first study to
comprehensively assess (neuro-)biological phenotypes of GBA
variants in PD. 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. © 2020 The Authors. Movement
Disorders published by Wiley Periodicals LLC on behalf of
International Parkinson and Movement Disorder Society.},
keywords = {Glucosylceramidase: genetics / Humans / Metabolomics /
Mutation: genetics / Neuroimaging / Parkinson Disease:
diagnostic imaging / Parkinson Disease: genetics / Phenotype
/ GBA (Other) / Parkinson's disease genetics (Other) /
metabolomics (Other) / multimodal functional neuroimaging
(Other)},
cin = {AG Boecker},
ddc = {610},
cid = {I:(DE-2719)1011202},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32853481},
doi = {10.1002/mds.28225},
url = {https://pub.dzne.de/record/154385},
}