Mapping striatal functional gradients and associated gene expression in Parkinson’s disease with continuous cognitive impairment
Abstract Cognitive impairment in Parkinson’s disease is closely tied to striatal dysfunction, yet the neurobiological interface between macroscale connectivity and molecular signatures remains unexplored. This study characterizes striatal gradient organization and its genetic underpinnings across PD...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-025-01002-2 |
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| _version_ | 1849688358703333376 |
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| author | Xiaolu Li Shuting Bu Huize Pang Hongmei Yu Mengwan Zhao Juzhou Wang Yu Liu Guoguang Fan |
| author_facet | Xiaolu Li Shuting Bu Huize Pang Hongmei Yu Mengwan Zhao Juzhou Wang Yu Liu Guoguang Fan |
| author_sort | Xiaolu Li |
| collection | DOAJ |
| description | Abstract Cognitive impairment in Parkinson’s disease is closely tied to striatal dysfunction, yet the neurobiological interface between macroscale connectivity and molecular signatures remains unexplored. This study characterizes striatal gradient organization and its genetic underpinnings across PD cognitive trajectories. We analyzed functional connectivity gradients in 126 PD patients (spanning the cognitive spectrum from normal cognition to dementia) and 40 healthy controls, correlating spatial patterns with neurotransmitter architecture and transcriptomic profiles. Three distinct striatal gradients emerged: Gradient 1 remains stable throughout disease progression and partially aligns with canonical striatal subdivisions. Gradient 2 represents a spatial continuum closely linked to dopaminergic innervation and becomes most pronounced in the dementia stage. Gradient 3 corresponds to cortico-striatal connectivity patterns implicated in both early and advanced cognitive deficits. Spatial transcriptomic and neuroimaging correlation analyses identified significant associations between cortico-striatal gradient disruptions and specific gene expression patterns. These findings provide valuable insights into striatal macro- and microstructural changes in PD and their role in cognitive impairment. |
| format | Article |
| id | doaj-art-4cd4758399054b1c9d9ce3cd0c435bab |
| institution | DOAJ |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-4cd4758399054b1c9d9ce3cd0c435bab2025-08-20T03:22:01ZengNature Portfolionpj Parkinson's Disease2373-80572025-05-0111111210.1038/s41531-025-01002-2Mapping striatal functional gradients and associated gene expression in Parkinson’s disease with continuous cognitive impairmentXiaolu Li0Shuting Bu1Huize Pang2Hongmei Yu3Mengwan Zhao4Juzhou Wang5Yu Liu6Guoguang Fan7Department of Radiology, The First Hospital of China Medical UniversityDepartment of Radiology, The First Hospital of China Medical UniversityDepartment of Radiology, The First Hospital of China Medical UniversityDepartment of Neurology, The First Hospital of China Medical UniversityDepartment of Radiology, The First Hospital of China Medical UniversityDepartment of Radiology, The First Hospital of China Medical UniversityDepartment of Radiology, The First Hospital of China Medical UniversityDepartment of Radiology, The First Hospital of China Medical UniversityAbstract Cognitive impairment in Parkinson’s disease is closely tied to striatal dysfunction, yet the neurobiological interface between macroscale connectivity and molecular signatures remains unexplored. This study characterizes striatal gradient organization and its genetic underpinnings across PD cognitive trajectories. We analyzed functional connectivity gradients in 126 PD patients (spanning the cognitive spectrum from normal cognition to dementia) and 40 healthy controls, correlating spatial patterns with neurotransmitter architecture and transcriptomic profiles. Three distinct striatal gradients emerged: Gradient 1 remains stable throughout disease progression and partially aligns with canonical striatal subdivisions. Gradient 2 represents a spatial continuum closely linked to dopaminergic innervation and becomes most pronounced in the dementia stage. Gradient 3 corresponds to cortico-striatal connectivity patterns implicated in both early and advanced cognitive deficits. Spatial transcriptomic and neuroimaging correlation analyses identified significant associations between cortico-striatal gradient disruptions and specific gene expression patterns. These findings provide valuable insights into striatal macro- and microstructural changes in PD and their role in cognitive impairment.https://doi.org/10.1038/s41531-025-01002-2 |
| spellingShingle | Xiaolu Li Shuting Bu Huize Pang Hongmei Yu Mengwan Zhao Juzhou Wang Yu Liu Guoguang Fan Mapping striatal functional gradients and associated gene expression in Parkinson’s disease with continuous cognitive impairment npj Parkinson's Disease |
| title | Mapping striatal functional gradients and associated gene expression in Parkinson’s disease with continuous cognitive impairment |
| title_full | Mapping striatal functional gradients and associated gene expression in Parkinson’s disease with continuous cognitive impairment |
| title_fullStr | Mapping striatal functional gradients and associated gene expression in Parkinson’s disease with continuous cognitive impairment |
| title_full_unstemmed | Mapping striatal functional gradients and associated gene expression in Parkinson’s disease with continuous cognitive impairment |
| title_short | Mapping striatal functional gradients and associated gene expression in Parkinson’s disease with continuous cognitive impairment |
| title_sort | mapping striatal functional gradients and associated gene expression in parkinson s disease with continuous cognitive impairment |
| url | https://doi.org/10.1038/s41531-025-01002-2 |
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