Multimodal MRI reveals impaired glymphatic function with choroid plexus enlargement and cerebrospinal fluid expansion in alzheimer’s disease

Abstract There is increasing evidence that cerebrospinal fluid (CSF) circulation plays a key role in the pathophysiology of Alzheimer’s disease (AD), although the underlying mechanisms remain poorly understood. This study evaluated CSF circulation in patients with AD using magnetic resonance imaging...

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Main Authors: Weiqi Lin, Huijuan Chen, Zhanrong Zhang, Yiying Zhang, Xingqun Wang, Yihao Guo, Haodong Qin, Tao Liu, Feng Chen
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-15923-8
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author Weiqi Lin
Huijuan Chen
Zhanrong Zhang
Yiying Zhang
Xingqun Wang
Yihao Guo
Haodong Qin
Tao Liu
Feng Chen
author_facet Weiqi Lin
Huijuan Chen
Zhanrong Zhang
Yiying Zhang
Xingqun Wang
Yihao Guo
Haodong Qin
Tao Liu
Feng Chen
author_sort Weiqi Lin
collection DOAJ
description Abstract There is increasing evidence that cerebrospinal fluid (CSF) circulation plays a key role in the pathophysiology of Alzheimer’s disease (AD), although the underlying mechanisms remain poorly understood. This study evaluated CSF circulation in patients with AD using magnetic resonance imaging (MRI)-derived measures, including choroid plexus (CP) volume, CSF volume, and diffusion tensor imaging along the perivascular space (DTI-ALPS) index. The study included 188 participants: 28 with AD, 40 with mild cognitive impairment (MCI), 66 with subjective cognitive decline (SCD), and 54 normal controls (NCs). Participants underwent structural T1-weighted MRI, diffusion tensor imaging, clinical assessment, and plasma biomarker analysis. After adjustments for age, sex, and education, group differences in the DTI-ALPS index, CP volume, and CSF volume were examined. Correlation and mediation analyses were conducted to assess the relationships of clinical parameters with DTI-ALPS index, CP volume, and CSF volume. The AD group exhibited a significantly lower DTI-ALPS index and higher CP and CSF volumes compared with the MCI, SCD, and NC groups. The DTI-ALPS index showed a strong negative correlation with both CP and CSF volumes, whereas CP volume was positively correlated with CSF volume. Mediation analysis revealed interactive relationships among the DTI-ALPS index, CP volume, and CSF volume. This study demonstrates that CSF circulation is disrupted in AD patients. Additionally, CP volume influences glymphatic drainage through its effects on CSF volume, indicating a potential role in AD pathophysiology.
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spelling doaj-art-ff4042a498ef4cd584be265fc74f92de2025-08-24T11:18:36ZengNature PortfolioScientific Reports2045-23222025-08-0115111210.1038/s41598-025-15923-8Multimodal MRI reveals impaired glymphatic function with choroid plexus enlargement and cerebrospinal fluid expansion in alzheimer’s diseaseWeiqi Lin0Huijuan Chen1Zhanrong Zhang2Yiying Zhang3Xingqun Wang4Yihao Guo5Haodong Qin6Tao Liu7Feng Chen8Hainan Affiliated Hospital of Hainan Medical University(Department of Radiology, Hainan General Hospital)Hainan Affiliated Hospital of Hainan Medical University(Department of Radiology, Hainan General Hospital)Hainan Affiliated Hospital of Hainan Medical University(Department of Radiology, Hainan General Hospital)Hainan Affiliated Hospital of Hainan Medical University(Department of Radiology, Hainan General Hospital)Hainan Affiliated Hospital of Hainan Medical University(Department of Radiology, Hainan General Hospital)Hainan Affiliated Hospital of Hainan Medical University(Department of Radiology, Hainan General Hospital)MR Research Collaboration, Siemens HealthineersHainan Affiliated Hospital of Hainan Medical UniversityHainan Affiliated Hospital of Hainan Medical University(Department of Radiology, Hainan General Hospital)Abstract There is increasing evidence that cerebrospinal fluid (CSF) circulation plays a key role in the pathophysiology of Alzheimer’s disease (AD), although the underlying mechanisms remain poorly understood. This study evaluated CSF circulation in patients with AD using magnetic resonance imaging (MRI)-derived measures, including choroid plexus (CP) volume, CSF volume, and diffusion tensor imaging along the perivascular space (DTI-ALPS) index. The study included 188 participants: 28 with AD, 40 with mild cognitive impairment (MCI), 66 with subjective cognitive decline (SCD), and 54 normal controls (NCs). Participants underwent structural T1-weighted MRI, diffusion tensor imaging, clinical assessment, and plasma biomarker analysis. After adjustments for age, sex, and education, group differences in the DTI-ALPS index, CP volume, and CSF volume were examined. Correlation and mediation analyses were conducted to assess the relationships of clinical parameters with DTI-ALPS index, CP volume, and CSF volume. The AD group exhibited a significantly lower DTI-ALPS index and higher CP and CSF volumes compared with the MCI, SCD, and NC groups. The DTI-ALPS index showed a strong negative correlation with both CP and CSF volumes, whereas CP volume was positively correlated with CSF volume. Mediation analysis revealed interactive relationships among the DTI-ALPS index, CP volume, and CSF volume. This study demonstrates that CSF circulation is disrupted in AD patients. Additionally, CP volume influences glymphatic drainage through its effects on CSF volume, indicating a potential role in AD pathophysiology.https://doi.org/10.1038/s41598-025-15923-8Cerebrospinal fluid circulationDTI-ALPSChoroid plexus volumeCerebrospinal fluid volumeAlzheimer’s disease
spellingShingle Weiqi Lin
Huijuan Chen
Zhanrong Zhang
Yiying Zhang
Xingqun Wang
Yihao Guo
Haodong Qin
Tao Liu
Feng Chen
Multimodal MRI reveals impaired glymphatic function with choroid plexus enlargement and cerebrospinal fluid expansion in alzheimer’s disease
Scientific Reports
Cerebrospinal fluid circulation
DTI-ALPS
Choroid plexus volume
Cerebrospinal fluid volume
Alzheimer’s disease
title Multimodal MRI reveals impaired glymphatic function with choroid plexus enlargement and cerebrospinal fluid expansion in alzheimer’s disease
title_full Multimodal MRI reveals impaired glymphatic function with choroid plexus enlargement and cerebrospinal fluid expansion in alzheimer’s disease
title_fullStr Multimodal MRI reveals impaired glymphatic function with choroid plexus enlargement and cerebrospinal fluid expansion in alzheimer’s disease
title_full_unstemmed Multimodal MRI reveals impaired glymphatic function with choroid plexus enlargement and cerebrospinal fluid expansion in alzheimer’s disease
title_short Multimodal MRI reveals impaired glymphatic function with choroid plexus enlargement and cerebrospinal fluid expansion in alzheimer’s disease
title_sort multimodal mri reveals impaired glymphatic function with choroid plexus enlargement and cerebrospinal fluid expansion in alzheimer s disease
topic Cerebrospinal fluid circulation
DTI-ALPS
Choroid plexus volume
Cerebrospinal fluid volume
Alzheimer’s disease
url https://doi.org/10.1038/s41598-025-15923-8
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