Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Choroid plexus remodeling linked to impaired CSF-mediated clearance and Alzheimer's disease progression.
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Yin Haolin, Deng Yuepeng, Lu ZiHao, Jiang Yu, Zuo Chao, Li Jianyu, Guo Linlin, Ying Binwu, Battaglia Giuseppe, Tian Xiaohe, Gong Qiyong, Alzheimer's Disease Neuroimaging Initiative (ADNI)
Аннотация
INTRODUCTION: Impaired cerebrospinal fluid (CSF) -mediated clearance has been implicated in Alzheimer's disease (AD), but how choroid plexus (ChP) remodeling relates to these processes in vivo remains incompletely understood.
METHODS: In a large ADNI cohort, we integrated structural magnetic resonance imaging (MRI), amyloid/tau positron emission tomography (PET), and diffusion tensor imaging (DTI) -derived analysis along the perivascular space (ALPS) to characterize ChP changes and their associations with ventricular measures, glymphatic marker, CSF biomarkers, and cognition across diagnostic stages. Our experiments in APP/PS1 mice complemented human analyses.
RESULTS: ChP volume increased with disease stage, while PET signal decreased. Larger ChP volume was associated with ventricular enlargement, a lower ALPS index, higher cortical amyloid/tau burden, and worse cognitive performance. Glymphatic impairment partially mediated ChP effects on cognition and pathology. APP/PS1 mice recapitulated the key ChP and glymphatic MRI phenotypes observed in humans, alongside altered expression and localization of key proteins.
DISCUSSION: ChP remodeling linked to impaired CSF-mediated clearance, highlighting its role as an early diagnostic and therapeutic target.
METHODS: In a large ADNI cohort, we integrated structural magnetic resonance imaging (MRI), amyloid/tau positron emission tomography (PET), and diffusion tensor imaging (DTI) -derived analysis along the perivascular space (ALPS) to characterize ChP changes and their associations with ventricular measures, glymphatic marker, CSF biomarkers, and cognition across diagnostic stages. Our experiments in APP/PS1 mice complemented human analyses.
RESULTS: ChP volume increased with disease stage, while PET signal decreased. Larger ChP volume was associated with ventricular enlargement, a lower ALPS index, higher cortical amyloid/tau burden, and worse cognitive performance. Glymphatic impairment partially mediated ChP effects on cognition and pathology. APP/PS1 mice recapitulated the key ChP and glymphatic MRI phenotypes observed in humans, alongside altered expression and localization of key proteins.
DISCUSSION: ChP remodeling linked to impaired CSF-mediated clearance, highlighting its role as an early diagnostic and therapeutic target.