Association of choroid plexus volume with white matter microstructure, glymphatic function, and peripheral systemic inflammation in Alzheimer’s disease

Abstract There has been growing attention to the role of choroid plexus (CP) in neurodegenerative diseases. However, its relationship with various pathophysiological changes in Alzheimer’s Disease (AD) remains unclear. The purpose of this study is to investigate the relationship between CP volume (C...

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Main Authors: Huwei Xia, Yijia Feng, Han Zhu, Danlu Yang, Chaoqun Wang, Zhipeng Wang, Hanyuan Zhang, Wenhao Pan, Yifan Zhao, for the Alzheimer’s Disease Neuroimaging Initiative, Weihong Song, Yili Wu
Format: Article
Language:English
Published: Nature Publishing Group 2025-07-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03432-1
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author Huwei Xia
Yijia Feng
Han Zhu
Danlu Yang
Chaoqun Wang
Zhipeng Wang
Hanyuan Zhang
Wenhao Pan
Yifan Zhao
for the Alzheimer’s Disease Neuroimaging Initiative
Weihong Song
Yili Wu
author_facet Huwei Xia
Yijia Feng
Han Zhu
Danlu Yang
Chaoqun Wang
Zhipeng Wang
Hanyuan Zhang
Wenhao Pan
Yifan Zhao
for the Alzheimer’s Disease Neuroimaging Initiative
Weihong Song
Yili Wu
author_sort Huwei Xia
collection DOAJ
description Abstract There has been growing attention to the role of choroid plexus (CP) in neurodegenerative diseases. However, its relationship with various pathophysiological changes in Alzheimer’s Disease (AD) remains unclear. The purpose of this study is to investigate the relationship between CP volume (CPV) and white matter microstructure, cognitive function, glymphatic function, and peripheral systemic inflammation in AD. A total of 1351 participants with cognitive impairment who had available 3 T MRI scans were included from ADNI. CPV was automatically segmented using Gaussian Mixture Model (GMM). The Mini-Mental State Examination (MMSE) was employed to assess cognitive function. PSMD and DTI-ALPS based on DTI sequence were used to reflect white matter microstructure and glymphatic system. Peripheral systemic inflammation was represented by the neutrophil-lymphocyte ratio (NLR). Group comparisons and correlations were adjusted for age, sex, education and APOE4 carrier status. Participants with AD exhibited larger CPV (p < 0.001), higher PSMD (p < 0.001) and NLR (p = 0.035), and lower DTI-ALPS (p < 0.001) compared to those with subjective cognitive decline (SCD). CP enlargement was independently associated with higher PSMD (β = 0.223, p < 0.001) and worse cognitive function both cross-sectionally (β = −0.212, p < 0.001) and longitudinally (β = −0.214, p < 0.001). Furthermore, PSMD partially mediates the impact of CP enlargement on the severity and progression of cognitive function. Partial correlation analysis revealed that CP enlargement was associated with higher NLR (r = 0.101, p = 0.001) and lower DTI-ALPS (r = −0.241, p < 0.001). These findings suggest that CPV may reflect underlying pathophysiological processes in AD and serve as a biomarker for white matter damage and cognitive impairment progression.
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spelling doaj-art-b35976dfa2854f5bbcf8367dea20b31a2025-08-20T03:42:07ZengNature Publishing GroupTranslational Psychiatry2158-31882025-07-011511910.1038/s41398-025-03432-1Association of choroid plexus volume with white matter microstructure, glymphatic function, and peripheral systemic inflammation in Alzheimer’s diseaseHuwei Xia0Yijia Feng1Han Zhu2Danlu Yang3Chaoqun Wang4Zhipeng Wang5Hanyuan Zhang6Wenhao Pan7Yifan Zhao8for the Alzheimer’s Disease Neuroimaging InitiativeWeihong Song9Yili Wu10Center for Geriatric Medicine, Zhejiang Key Laboratory of Alzheimer’s Disease, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Provincial Clinical Research Center for Mental Health, Institute of Aging, Wenzhou Medical UniversityCenter for Geriatric Medicine, Zhejiang Key Laboratory of Alzheimer’s Disease, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Provincial Clinical Research Center for Mental Health, Institute of Aging, Wenzhou Medical UniversityCenter for Geriatric Medicine, Zhejiang Key Laboratory of Alzheimer’s Disease, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Provincial Clinical Research Center for Mental Health, Institute of Aging, Wenzhou Medical UniversityCenter for Geriatric Medicine, Zhejiang Key Laboratory of Alzheimer’s Disease, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Provincial Clinical Research Center for Mental Health, Institute of Aging, Wenzhou Medical UniversityCenter for Geriatric Medicine, Zhejiang Key Laboratory of Alzheimer’s Disease, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Provincial Clinical Research Center for Mental Health, Institute of Aging, Wenzhou Medical UniversityCenter for Geriatric Medicine, Zhejiang Key Laboratory of Alzheimer’s Disease, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Provincial Clinical Research Center for Mental Health, Institute of Aging, Wenzhou Medical UniversityCenter for Geriatric Medicine, Zhejiang Key Laboratory of Alzheimer’s Disease, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Provincial Clinical Research Center for Mental Health, Institute of Aging, Wenzhou Medical UniversityCenter for Geriatric Medicine, Zhejiang Key Laboratory of Alzheimer’s Disease, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Provincial Clinical Research Center for Mental Health, Institute of Aging, Wenzhou Medical UniversityCenter for Geriatric Medicine, Zhejiang Key Laboratory of Alzheimer’s Disease, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Provincial Clinical Research Center for Mental Health, Institute of Aging, Wenzhou Medical UniversityCenter for Geriatric Medicine, Zhejiang Key Laboratory of Alzheimer’s Disease, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Zhejiang Provincial Clinical Research Center for Mental Health, Institute of Aging, Wenzhou Medical UniversityWenzhou Key Laboratory of Basic and Translational Research for Mental disorders, Zhejiang Provincial Clinical Research Center for Mental Health, Key Laboratory of Alzheimer’s Disease of Zhejiang Province, School of Mental Health and The Affiliated Wenzhou Kangning Hospital, Institute of Aging, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical UniversityAbstract There has been growing attention to the role of choroid plexus (CP) in neurodegenerative diseases. However, its relationship with various pathophysiological changes in Alzheimer’s Disease (AD) remains unclear. The purpose of this study is to investigate the relationship between CP volume (CPV) and white matter microstructure, cognitive function, glymphatic function, and peripheral systemic inflammation in AD. A total of 1351 participants with cognitive impairment who had available 3 T MRI scans were included from ADNI. CPV was automatically segmented using Gaussian Mixture Model (GMM). The Mini-Mental State Examination (MMSE) was employed to assess cognitive function. PSMD and DTI-ALPS based on DTI sequence were used to reflect white matter microstructure and glymphatic system. Peripheral systemic inflammation was represented by the neutrophil-lymphocyte ratio (NLR). Group comparisons and correlations were adjusted for age, sex, education and APOE4 carrier status. Participants with AD exhibited larger CPV (p < 0.001), higher PSMD (p < 0.001) and NLR (p = 0.035), and lower DTI-ALPS (p < 0.001) compared to those with subjective cognitive decline (SCD). CP enlargement was independently associated with higher PSMD (β = 0.223, p < 0.001) and worse cognitive function both cross-sectionally (β = −0.212, p < 0.001) and longitudinally (β = −0.214, p < 0.001). Furthermore, PSMD partially mediates the impact of CP enlargement on the severity and progression of cognitive function. Partial correlation analysis revealed that CP enlargement was associated with higher NLR (r = 0.101, p = 0.001) and lower DTI-ALPS (r = −0.241, p < 0.001). These findings suggest that CPV may reflect underlying pathophysiological processes in AD and serve as a biomarker for white matter damage and cognitive impairment progression.https://doi.org/10.1038/s41398-025-03432-1
spellingShingle Huwei Xia
Yijia Feng
Han Zhu
Danlu Yang
Chaoqun Wang
Zhipeng Wang
Hanyuan Zhang
Wenhao Pan
Yifan Zhao
for the Alzheimer’s Disease Neuroimaging Initiative
Weihong Song
Yili Wu
Association of choroid plexus volume with white matter microstructure, glymphatic function, and peripheral systemic inflammation in Alzheimer’s disease
Translational Psychiatry
title Association of choroid plexus volume with white matter microstructure, glymphatic function, and peripheral systemic inflammation in Alzheimer’s disease
title_full Association of choroid plexus volume with white matter microstructure, glymphatic function, and peripheral systemic inflammation in Alzheimer’s disease
title_fullStr Association of choroid plexus volume with white matter microstructure, glymphatic function, and peripheral systemic inflammation in Alzheimer’s disease
title_full_unstemmed Association of choroid plexus volume with white matter microstructure, glymphatic function, and peripheral systemic inflammation in Alzheimer’s disease
title_short Association of choroid plexus volume with white matter microstructure, glymphatic function, and peripheral systemic inflammation in Alzheimer’s disease
title_sort association of choroid plexus volume with white matter microstructure glymphatic function and peripheral systemic inflammation in alzheimer s disease
url https://doi.org/10.1038/s41398-025-03432-1
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