Phenotypic effect of GBA1 variants in individuals with and without Parkinson's disease: The RAPSODI study.

Autor:	Toffoli M; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA., Chohan H; Preventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London, UK., Mullin S; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Faculty of Health, University of Plymouth, Plymouth PL4 8AA, UK., Jesuthasan A; Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK., Yalkic S; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA., Koletsi S; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA., Menozzi E; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA., Rahall S; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK., Limbachiya N; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK., Loefflad N; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA., Higgins A; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK., Bestwick J; Preventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London, UK., Lucas-Del-Pozo S; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA., Fierli F; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA., Farbos A; Biosciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK., Mezabrovschi R; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA., Lee-Yin C; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA., Schrag A; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK., Moreno-Martinez D; Lysosomal Storage Disorders Unit, Royal Free Hospital NHS Foundation Trust and University College London, London, UK., Hughes D; Lysosomal Storage Disorders Unit, Royal Free Hospital NHS Foundation Trust and University College London, London, UK., Noyce A; Preventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London, UK., Colclough K; Exeter Genomics Laboratory, Royal Devon University Healthcare NHS Trust, Exeter, UK., Jeffries AR; Biosciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK., Proukakis C; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA., Schapira AHV; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA. Electronic address: a.schapira@ucl.ac.uk.
Jazyk:	angličtina
Zdroj:	Neurobiology of disease [Neurobiol Dis] 2023 Nov; Vol. 188, pp. 106343. Date of Electronic Publication: 2023 Nov 03.
DOI:	10.1016/j.nbd.2023.106343
Abstrakt:	Background: Variants in the GBA1 gene cause the lysosomal storage disorder Gaucher disease (GD). They are also risk factors for Parkinson's disease (PD), and modify the expression of the PD phenotype. The penetrance of GBA1 variants in PD is incomplete, and the ability to determine who among GBA1 variant carriers are at higher risk of developing PD, would represent an advantage for prognostic and trial design purposes. Objectives: To compare the motor and non-motor phenotype of GBA1 carriers and non-carriers. Methods: We present the cross-sectional results of the baseline assessment from the RAPSODI study, an online assessment tool for PD patients and GBA1 variant carriers. The assessment includes clinically validated questionnaires, a tap-test, the University of Pennsyllvania Smell Identification Test and cognitive tests. Additional, homogeneous data from the PREDICT-PD cohort were included. Results: A total of 379 participants completed all parts of the RAPSODI assessment (89 GBA1-negative controls, 169 GBA1-negative PD, 47 GBA1-positive PD, 47 non-affected GBA1 carriers, 27 GD). Eighty-six participants were recruited through PREDICT-PD (43 non-affected GBA1 carriers and 43 GBA1-negative controls). GBA1-positive PD patients showed worse performance in visual cognitive tasks and olfaction compared to GBA1-negative PD patients. No differences were detected between non-affected GBA1 carriers carriers and GBA1-negative controls. No phenotypic differences were observed between any of the non-PD groups. Conclusions: Our results support previous evidence that GBA1-positive PD has a specific phenotype with more severe non-motor symptoms. However, we did not reproduce previous findings of more frequent prodromal PD signs in non-affected GBA1 carriers. Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest or financial issues to declare in relation to this manuscript. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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