Modelling cholinergic and dopaminergic function over time in Parkinson’s disease with and without GBA1 variants
Parkinson's Disease (PD) patients carrying GBA1-variants (GBA-PD) often show a faster cognitive decline, suggesting accelerated cholinergic degeneration. This study investigated changes over time in whole-brain cholinergic innervation within the context of dopaminergic changes and clinical outcomes in GBA-PD versus non-GBA-PD. 171 PD participants (44 GBA-PD, 127 non-GBA-PD) underwent clinical and neuropsychological assessments, brain MRI, <sup>18</sup>F-fluoroethoxy-benzovesamicol (<sup>18</sup>F-FEOBV) PET (cholinergic) and 3,4-dihydroxy-6-<sup>18</sup>F-fluoro-I-phenylalanine (<sup>18</sup>F-FDOPA) PET (dopaminergic) imaging. GBA-PD participants showed worse executive functioning than non-GBA-PD. Voxel-wise linear mixed-effects models showed that GBA-PD exhibited lower <sup>18</sup>F-FEOBV binding in the right precentral and middle frontal gyrus, independent of age and sex, despite similar cholinergic decline over time. No GBA1-related differences were found in dopaminergic signal or its progression. Age and time since diagnosis were associated with progressive cholinergic and dopaminergic denervation in all patients. This first dual-tracer longitudinal PET study highlights early cholinergic involvement in GBA-PD and supports further evaluation of <sup>18</sup>F-FEOBV PET as biomarker.
Authors
- Ingeborg Goethals (ORCID: https://orcid.org/0000-0001-7432-4452)
- Jeffrey M. Boertien (ORCID: https://orcid.org/0000-0002-9664-1771)
- Éric Meyer (ORCID: https://orcid.org/0000-0002-3161-8597)
- Teus van Laar (ORCID: https://orcid.org/0000-0001-5088-480X)
- Sanne K. Meles (ORCID: https://orcid.org/0000-0002-5505-3527)
- Giulia Carli (ORCID: https://orcid.org/0000-0001-7216-2031)
- Emile d’Angremont (ORCID: https://orcid.org/0000-0002-5468-8811)
- Harm J. van der Horn (ORCID: https://orcid.org/0000-0001-9923-0866)
- Anne C. Slomp (ORCID: https://orcid.org/0000-0002-1685-3986)
- Sygrid van der Zee (ORCID: https://orcid.org/0000-0002-4244-369X)
- Sofie Slingerland (ORCID: https://orcid.org/0000-0001-7443-4918)
Institutions
- University Medical Center Groningen (NL)
- University of Groningen (NL)
- University of Michigan (US)
- Ghent University (BE)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2025-11-12
- DOI
- https://doi.org/10.1038/s41531-025-01160-3
- Primary Topic
- Lysosomal Storage Disorders Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00