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August 19, 2025Open Access

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

WLWeiqi LinHainan General Hospital HCHuijuan ChenHainan Medical University ZZZhanrong ZhangHainan General Hospital

Key Points

AD patients show impaired glymphatic function with impaired cerebrospinal fluid circulation, impacting overall brain health.
Significant differences were noted in the DTI-ALPS index, CP volume, and CSF volume across AD, mild cognitive impairment, subjective cognitive decline, and normal controls.
The study utilized advanced MRI techniques to explore choroid plexus enlargement, cerebrospinal fluid expansion, and their relationships with clinical measures.
Understanding these mechanisms may help address Alzheimer’s disease’s pathophysiology, indicating areas for future research and intervention.

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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