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Updated: Mar 8, 2026
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Microglial activation in Parkinson's disease using [18F]-FEPPA
Christine Ghadery1,2, Yuko Koshimori1,2, Sarah Coakeley1,2
1Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
Background:
Neuroinflammatory processes including activated microglia have been reported to play an important role in Parkinson's disease (PD). Increased expression of translocator protein (TSPO) has been observed after brain injury and inflammation in neurodegenerative diseases. Positron emission tomography (PET) radioligand targeting TSPO allows for the quantification of neuroinflammation in vivo.
Methods:
Based on the genotype of the rs6791 polymorphism in the TSPO gene, we included 25 mixed-affinity binders (MABs) (14 PD patients and 11 age-matched healthy controls (HC)) and 27 high-affinity binders (HABs) (16 PD patients and 11 age-matched HC) to assess regional differences in the second-generation radioligand [18F]-FEPPA between PD patients and HC. FEPPA total distribution volume (V T) values in cortical as well as subcortical brain regions were derived from a two-tissue compartment model with arterial plasma as an input function.
Results:
Our results revealed a significant main effect of genotype on [18F]-FEPPA V T in every brain region, but no main effect of disease or disease × genotype interaction in any brain region. The overall percentage difference of the mean FEPPA V T between HC-MABs and HC-HABs was 32.6% (SD = 2.09) and for PD-MABs and PD-HABs was 43.1% (SD = 1.21).
Conclusions:
Future investigations are needed to determine the significance of [18F]-FEPPA as a biomarker of neuroinflammation as well as the importance of the rs6971 polymorphism and its clinical consequence in PD.
Insights
Neuroinflammation in Parkinson's disease (PD) was assessed using [18F]-FEPPA PET scans. TSPO gene polymorphism significantly impacted tracer binding, but not PD status itself.
Area of Science:
- Neuroscience
- Radiochemistry
- Medical Imaging
Background:
- Neuroinflammation, characterized by activated microglia, is implicated in Parkinson's disease (PD).
- Translocator protein (TSPO) expression increases with brain injury and neurodegeneration.
- Positron emission tomography (PET) targeting TSPO enables in vivo quantification of neuroinflammation.
Purpose of the Study:
- To evaluate regional differences in [18F]-FEPPA binding between PD patients and healthy controls (HC).
- To assess the influence of TSPO gene rs6971 polymorphism on [18F]-FEPPA binding in PD and HC.
Main Methods:
- Inclusion of 25 mixed-affinity binders (MABs) and 27 high-affinity binders (HABs) based on rs6971 genotype.
- PET imaging with the TSPO-targeting radioligand [18F]-FEPPA.
- Quantification of total distribution volume (VT) using a two-tissue compartment model with arterial input.
Main Results:
- A significant main effect of TSPO genotype on [18F]-FEPPA VT was observed across all brain regions.
- No significant main effect of PD or disease × genotype interaction on [18F]-FEPPA VT was found.
- Mean [18F]-FEPPA VT differences between MABs and HABs were 32.6% in HC and 43.1% in PD patients.
Conclusions:
- TSPO genotype significantly influences [18F]-FEPPA binding, irrespective of Parkinson's disease status.
- Further research is required to establish [18F]-FEPPA as a reliable neuroinflammation biomarker in PD.
- The clinical significance of the rs6971 polymorphism in PD warrants additional investigation.
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