Multimodal neuroimaging elucidates the posterior-to-anterior gradient of nigrostriatal degeneration in Parkinson’s disease
10 affiliations
- 1Department of Nuclear Medicine/PET Center, Huashan Hospital, Fudan University
- 2School of Medicine, Shanghai University
- 3Department of Neurology, Huashan Hospital, Fudan University
- 4United Imaging Healthcare Co., Ltd., Chengbei Road
- 5Institute for Biomedical Engineering, University, and ETH Zurich, Institute for Regenerative of Medicine, University of Zurich
- 6Department of Psychiatry and Psychotherapy, Marburg University
- 7Department of Neurology, Marburg University
- 8Department of Nuclear Medicine, Inselspital, University of Bern
- 9Beijing United Imaging Healthcare Co., Ltd.
- 10Institute of Biomedical Engineering, School of Life Sciences, Shanghai University
Abstract
Parkinson’s disease (PD) exhibits a characteristic posterior-to-anterior gradient of striatal dopamine loss, yet the underlying upstream mechanisms remain unclear. We combined in vivo ¹⁸F-FPCIT dopamine transporter (DaT) PET/MRI, quantitative susceptibility mapping, and diffusion MRI tractography in 48 PD patients and 10 healthy controls to test whether substantia nigra pars compacta (SNc) iron and microstructural disruption mediate posterior putaminal vulnerability. PD patients showed marked posterior putamen (pPut) DaT reduction (~60%) and elevated SNc iron. SNc iron negatively correlated with striatal DaT availability, and nigrostriatal pathways to the pPut exhibited higher axial diffusivity. Serial mediation analyses demonstrated that SNc iron indirectly impaired striatal DaT function via reduced SNc DaT binding. Putaminal DaT-SBR robustly discriminated PD from controls (AUC 0.93–0.96), exceeding caudate performance. Transgenic and α-synuclein preformed fibril mouse models provided qualitative anatomical support. These findings identify SNc iron–related degeneration as a key driver of posterior striatal vulnerability in PD.
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BibTeX
@article{lin2026multimodal,
title = {{Multimodal neuroimaging elucidates the posterior-to-anterior gradient of nigrostriatal degeneration in Parkinson’s disease}},
author = {Huamei Lin and Ying Zhang and Yixin Zhao and Yiman Wei and Benjamin F. Combes and Martin T. Henrich and Fanni F. Geibl and Wolfgang H. Oertel and Kuangyu Shi and Axel Rominger and Ping Wu and Jingjie Ge and Jing Wang and Jiaying Lu and Zizhao Ju and Qian Xu and Huiwei Zhang and Yunhao Yang and Zengping Lin and Yang Yang and Yihui Guan and Fengtao Liu and Jian Wang and Jiehui Jiang and Ruiqing Ni and Chuantao Zuo},
journal = {npj Parkinson's Disease},
year = {2026},
month = jul,
doi = {10.1038/s41531-026-01456-y},
url = {https://doi.org/10.1038/s41531-026-01456-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multimodal neuroimaging elucidates the posterior-to-anterior gradient of nigrostriatal degeneration in Parkinson’s disease
AU - Huamei Lin
AU - Ying Zhang
AU - Yixin Zhao
AU - Yiman Wei
AU - Benjamin F. Combes
AU - Martin T. Henrich
AU - Fanni F. Geibl
AU - Wolfgang H. Oertel
AU - Kuangyu Shi
AU - Axel Rominger
AU - Ping Wu
AU - Jingjie Ge
AU - Jing Wang
AU - Jiaying Lu
AU - Zizhao Ju
AU - Qian Xu
AU - Huiwei Zhang
AU - Yunhao Yang
AU - Zengping Lin
AU - Yang Yang
AU - Yihui Guan
AU - Fengtao Liu
AU - Jian Wang
AU - Jiehui Jiang
AU - Ruiqing Ni
AU - Chuantao Zuo
PY - 2026
DA - 2026/07/01
JO - npj Parkinson's Disease
DO - 10.1038/s41531-026-01456-y
UR - https://doi.org/10.1038/s41531-026-01456-y
AB - Parkinson’s disease (PD) exhibits a characteristic posterior-to-anterior gradient of striatal dopamine loss, yet the underlying upstream mechanisms remain unclear. We combined in vivo ¹⁸F-FPCIT dopamine transporter (DaT) PET/MRI, quantitative susceptibility mapping, and diffusion MRI tractography in 48 PD patients and 10 healthy controls to test whether substantia nigra pars compacta (SNc) iron and microstructural disruption mediate posterior putaminal vulnerability. PD patients showed marked posterior putamen (pPut) DaT reduction (~60%) and elevated SNc iron. SNc iron negatively correlated with striatal DaT availability, and nigrostriatal pathways to the pPut exhibited higher axial diffusivity. Serial mediation analyses demonstrated that SNc iron indirectly impaired striatal DaT function via reduced SNc DaT binding. Putaminal DaT-SBR robustly discriminated PD from controls (AUC 0.93–0.96), exceeding caudate performance. Transgenic and α-synuclein preformed fibril mouse models provided qualitative anatomical support. These findings identify SNc iron–related degeneration as a key driver of posterior striatal vulnerability in PD.
SN - 2373-8057
ER -