Objective: To describe the relationships between dopaminergic and cholinergic terminal deficits in Progressive Supranuclear Palsy (PSP) relative to age-matched Normal controls (NC).

Background: There is loss of both dopaminergic and cholinergic terminals in PSP subjects. The in vivo regional relationships between these deficits and combined-synergistic effects on clinical features in PSP is underexamined. Our previous studies using vesicular acetylcholine transporter(VAChT) [¹⁸F]FEOBV PET showed cholinergic terminal deficits in the prefrontal cortex, anterior insulae, temporal pole, striatal subregions, brainstem, and cerebellum¹. Prior imaging studies examining dopaminergic changes focused predominantly on the striatum while extra-striatal changes remain largely unexplored^2–4. Our current study uses a multimodal imaging approach to assess whole-brain changes in integrity and intermodal coupling of cholinergic and dopaminergic changes in PSP.

Method: Six probable PSP patients (age: 74.20±4.26; 6M/0F) and 15 NC (70.13±6.45; 8M/7F) underwent dopamine transporter (DAT) [¹¹C]PE2I, VAChT [¹⁸F]FEOBV PET, and MR imaging. PSP diagnosis was based on the 2017 MDS criteria⁵. Coupled images between cholinergic and dopaminergic tracer studies were computed using the voxel-wise intermodal coupling (IMCo) method⁶. Individual PET modality and IMCo images were compared between PSP and NC using SPM12.

Results: Extensive and regionally distinct deficits of dopaminergic and cholinergic terminals were observed in PSP relative to controls. Dopaminergic terminals were reduced in the striata, pallidum, amygdala, hippocampus, insula, dorsal brainstem and Rolandic operculum. Cholinergic terminals were reduced in the locus coeruleus region, raphe nuclei, pedunculopontine nucleus-laterodorsal tegmental complex, thalamus, cerebellum, and primarily right-lateralized parietal, temporal, and occipital cortices, and in prefrontal cortex/cingulum. IMCo coupling between cholinergic and dopaminergic innervation of PSP patients was reduced primarily in the basal ganglia, extending to insular and temporal cortices.

Conclusion: Our combined PET imaging study indicates that PSP is characterized by extensive, partially coupled loss of both dopaminergic and cholinergic terminals. Future studies are needed to determine whether coupled deficits reflect joint terminal loss or decay of cholinergic upregulation in PSP.

Figure 1.

References: 1. Kanel, P. et al. Differential cholinergic systems’ changes in progressive supranuclear palsy versus Parkinson’s disease: an exploratory analysis. J. Neural Transm. (Vienna) 129, 1469–1479 (2022).
2. Chen, Q.-S. et al. Dopamine transporter imaging in progressive supranuclear palsy: Severe but nonspecific to subtypes. Acta Neurol. Scand. 146, 237–245 (2022).
3. Chen, M.-J. et al. Striatal dopaminergic lesions contributed to the disease severity in progressive supranuclear palsy. Front. Aging Neurosci. 14, 998255 (2022).
4. Ma, J.-H. et al. Striatal and extrastriatal monoaminergic disruption in progressive supranuclear palsy. Mov. Disord. 39, 847–854 (2024).
5. Höglinger, G. U. et al. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov. Disord. 32, 853–864 (2017).
6. Hu, F. et al. Voxel-wise intermodal coupling analysis of two or more modalities using local covariance decomposition. Hum. Brain Mapp. 43, 4650–4663 (2022)

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/coupling-of-cholinergic-and-dopaminergic-terminal-loss-in-progressive-supranuclear-palsy-a-multimodal-18ffeobv-and-11cpe2i-study/