Striatal dopaminergic lesions contributed to the disease severity in progressive supranuclear palsy

Ming-Jia Chen; Jia-Ying Lu; Xin-Yi Li; Fang-Yang Jiao; Chuan-Tao Zuo; Jian Wang; Feng-Tao Liu; Yu-Jie Yang

doi:10.3389/fnagi.2022.998255

Striatal dopaminergic lesions contributed to the disease severity in progressive supranuclear palsy

Front Aging Neurosci. 2022 Aug 24:14:998255. doi: 10.3389/fnagi.2022.998255. eCollection 2022.

Authors

Ming-Jia Chen¹, Jia-Ying Lu², Xin-Yi Li¹, Fang-Yang Jiao², Chuan-Tao Zuo^{2

3}, Jian Wang¹, Feng-Tao Liu¹, Yu-Jie Yang^{1

4}

Affiliations

¹ Department of Neurology, National Research Center for Aging and Medicine, National Center for Neurological Disorders, and State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University, Shanghai, China.
² PET Center, National Center for Neurological Disorders, and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
³ Human Phenome Institute, Fudan University, Shanghai, China.
⁴ Key Laboratory of Arrhythmias, Ministry of Education, Department of Medical Genetics, Shanghai East Hospital, School of Medicine, Tonji University, Shanghai, China.

Abstract

Background: Reduced dopamine transporter (DAT) binding in the striatum has been reported in patients with progressive supranuclear palsy (PSP). However, the relationship between striatal dopaminergic lesions and the disease severity of PSP remains to be explored.

Objective: To investigate the contributions of striatal dopaminergic lesions to the disease severity of PSP.

Methods: One hundred patients with clinically diagnosed PSP were consecutively enrolled in this study. The disease severity was systemically assessed using the PSP rating scale (PSPrs), and the dopaminergic lesions were assessed using the ¹¹C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane positron emission tomography (¹¹C-CFT PET) imaging. To explore the correlations between striatal DAT bindings and the disease severity, both the region-wise and voxel-wise analysis were adopted. Partial correlations and multiple linear regressions were performed to investigate the contribution of striatal dopaminergic lesions to the disease severity in PSP.

Results: Sixty-three patients of PSP with Richardson's syndrome (PSP-RS) and 37 patients with PSP-non-RS were finally included. The disease severity in PSP-RS was much heavier than that in the PSP-non-RS. The DAT bindings in the caudate and anterior putamen correlated significantly with the PSPrs total scores, mainly in the domains of history, mentation, bulbar, and ocular motor symptoms. The striatal DAT bindings (caudate) contributed significantly to the disease severity of PSP, independent of the motor, cognition, emotion and behavioral dysfunctions.

Conclusion: Our study highlighted the independent contribution of striatal dopaminergic lesions to the disease severity in PSP.

Keywords: caudate; disease severity; dopamine transporter; position emission tomography; progressive supranuclear palsy.