> Details

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

GBA Variants in Parkinson's Disease: Clinical, Metabolomic, and Multimodal Neuroimaging Phenotypes

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: GBA Variants in Parkinson's Disease: Clinical, Metabolomic, and Multimodal Neuroimaging Phenotypes
  • Contributor: Greuel, Andrea; Trezzi, Jean‐Pierre; Glaab, Enrico; Ruppert, Marina C.; Maier, Franziska; Jäger, Christian; Hodak, Zdenka; Lohmann, Katja; Ma, Yilong; Eidelberg, David; Timmermann, Lars; Hiller, Karsten; Tittgemeyer, Marc; Drzezga, Alexander; Diederich, Nico; Eggers, Carsten
  • imprint: Wiley, 2020
  • Published in: Movement Disorders
  • Language: English
  • DOI: 10.1002/mds.28225
  • ISSN: 0885-3185; 1531-8257
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Alterations in the <jats:italic>GBA</jats:italic> gene (NM_000157.3) are the most important genetic risk factor for Parkinson's disease (PD). Biallelic <jats:italic>GBA</jats:italic> mutations cause the lysosomal storage disorder Gaucher's disease. The <jats:italic>GBA</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>This study analyzed clinical, neuropsychological, metabolic, and neuroimaging phenotypes of patients with PD carrying the <jats:italic>GBA</jats:italic> variants p.E365K and p.T408M.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p><jats:italic>GBA</jats:italic> was sequenced in 56 patients with mid‐stage PD. Carriers of <jats:italic>GBA</jats:italic> 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‐[<jats:sup>18</jats:sup>F]fluoro‐L‐Dopa positron emission tomography (PET), [<jats:sup>18</jats:sup>F]fluorodeoxyglucose PET, and resting‐state functional magnetic resonance imaging were performed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Sequence analysis detected 13 heterozygous <jats:italic>GBA</jats:italic> variant carriers (7 with p.E365K, 6 with p.T408M). One patient carried a <jats:italic>GBA</jats:italic> 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; [<jats:sup>18</jats:sup>F]fluorodeoxyglucose PET and functional magnetic resonance imaging showed similarities with Lewy body dementia and PD dementia in carriers.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>This is the first study to comprehensively assess (neuro‐)biological phenotypes of <jats:italic>GBA</jats:italic> 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. <jats:italic>Movement Disorders</jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society</jats:p></jats:sec>