Choroid plexus remodeling linked to impaired CSF‐mediated clearance and Alzheimer's disease progression
Haolin Yin, Yuepeng Deng, ZiHao Lu, Yu Jiang, Chao Zuo, Jianyu Li, Linlin Guo, Binwu Ying, Giuseppe Battaglia, Xiaohe Tian, Qiyong Gong,Abstract
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.