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Updated: Jun 28, 2025
Dynamic Digital Biomarkers of Motor and Cognitive Function in Parkinson's Disease
Published on: July 24, 2019
Glutamate Signaling in Patients With Parkinson Disease With REM Sleep Behavior Disorder
Christopher E J Doppler1, Aline Seger1, Ezequiel Farrher1
1From the Cognitive Neuroscience (C.E.J.D., A.S., L.H., G.R.F., M.S.), Institute of Neuroscience and Medicine (INM-3), Forschungszentrum Jülich; Department of Neurology (C.E.J.D., A.S., L.H., G.R.F., M.S.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Köln; Institute of Neuroscience and Medicine (INM-4) (E.F., C.R.B., A.G., N.J.S., C.W.L., K.-J.L.), Forschungszentrum Jülich; Department of Nuclear Medicine (C.P.F., K.-J.L.), RWTH University Hospital, Aachen; Institute of Medical Statistics and Computational Biology (M.H.), Faculty of Medicine and University Hospital of Cologne, University of Cologne; Faculty of Medicine (A.G.), RWTH Aachen University, Germany; Engineering Physics Department (A.G.), Georgian Technical University, Tbilisi, Georgia; Institute of Neuroscience and Medicine (INM-11) (N.J.S.), Molecular Neuroscience and Neuroimaging, JARA, Forschungszentrum Jülich; JARA-BRAIN-Translational Medicine (N.J.S.), Aachen; Department of Neurology (N.J.S.), RWTH Aachen University; and Institute of Neuroscience and Medicine (INM-5) (B.N.), Forschungszentrum Jülich, Germany.
Background And Objectives:
Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotransmitter systems remain elusive.
Methods:
Combining magnetic resonance (MR) spectroscopy and [11C]ABP688 PET on a PET/MR hybrid system, we simultaneously investigated two different mechanisms of glutamate signaling in patients with PD. Patients were grouped according to their RBD status in overnight video-polysomnography and compared with age-matched and sex-matched healthy control (HC) participants. Total volumes of distribution (VT) of [11C]ABP688 were estimated with metabolite-corrected plasma concentrations during steady-state conditions between 45 and 60 minutes of the scan following a bolus-infusion protocol. Glutamate, glutamine, and glutathione levels were investigated with single-voxel stimulated echo acquisition mode MR spectroscopy of the left basal ganglia.
Results:
We measured globally elevated VT of [11C]ABP688 in 16 patients with PD and RBD compared with 17 patients without RBD and 15 HC participants (F(2,45) = 5.579, p = 0.007). Conversely, glutamatergic metabolites did not differ between groups and did not correlate with the regional VT of [11C]ABP688. VT of [11C]ABP688 correlated with the amount of REM sleep without atonia (F(1,42) = 5.600, p = 0.023) and with dopaminergic treatment response in patients with PD (F(1,30) = 5.823, p = 0.022).
Discussion:
Our results suggest that patients with PD and RBD exhibit altered glutamatergic signaling indicated by higher VT of [11C]ABP688 despite unaffected glutamate levels. The imbalance of glutamate receptors and MR spectroscopy glutamate metabolite levels indicates a novel mechanism contributing to the heterogeneity of PD and warrants further investigation of drugs targeting mGluR5.
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