Choroid plexus free-water correlates with glymphatic function in Alzheimer's disease.

Introduction: Free-water imaging of the choroid plexus (CP) may improve the evaluation of Alzheimer's disease (AD).

Methods: Our study investigated the role of free-water fraction (FWf) of CP in AD among 216 participants (133 Aβ+ participants and 83 Aβ- controls) enrolled in the NeuroBank-Dementia cohort at Ruijin Hospital (RJNB-D). The Alzheimer's Disease Neuroimaging Initiative dataset was used for external validation.

Results: At baseline, Aβ+ participants showed higher CP FWf, increased white matter hyperintensity (WMH) volume, and decreased diffusion tensor image analysis along the perivascular space (DTI-ALPS). In Aβ+ participants, DTI-ALPS mediated the association between CP FWf and periventricular WMH. CP FWf was associated with cortical tau accumulation, synaptic loss, hippocampal and cortical atrophy, and cognitive performance. During follow-up, CP FWf increased faster in Aβ+ participants than controls.

Discussion: Elevated CP FWf indicated impaired glymphatic function and AD neurodegeneration, and can be a sensitive biomarker for AD progression. The study was registered on ClinicalTrials.gov (NCT05623124).

Highlights: This cohort study found higher free-water fraction (FWf) of the choroid plexus (CP) in amyloid beta (Aβ)+ participants. CP FWf was related to glymphatic function, brain atrophy, tau burden, synaptic loss, and cognition. Aβ+ participants showed faster growth of CP FWf than Aβ- controls during follow-up. The growth rate of CP FWf exceeded that of white matter lesion and tau accumulation in Aβ+ participants. CP FWf can serve as a sensitive imaging marker of glymphatic function and Alzheimer's disease progression.