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@ARTICLE{Greuel:889142,
      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     = {FZJ-2021-00067},
      pages        = {2201 - 2210},
      year         = {2020},
      abstract     = {Background: 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.Objective: This study analyzed
                      clinical, neuropsychological, metabolic, and neuroimaging
                      phenotypes of patients with PD carrying the GBA variants
                      p.E365K and p.T408M.Methods: 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.Results: 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.Conclusions: 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.},
      cin          = {INM-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-2-20090406},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572) / 573 -
                      Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-572 / G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {32853481},
      UT           = {WOS:000562918700001},
      doi          = {10.1002/mds.28225},
      url          = {https://juser.fz-juelich.de/record/889142},
}