Choroid Plexus Free-Water Correlates with Glymphatic function in Alzheimer Disease: The RJNB-D Study

The free water imaging of choroid plexus (CP) may improve the evaluation of Alzheimer's disease (AD). Our study investigated the role of free water fraction (FWf) of CP in AD by including 216 participants (133 Aβ + participants and 83 Aβ- controls) continuously enrolled in the NeuroBank-Dementia cohort at Ruijin Hospital (RJNB-D). At baseline, Aβ + participants showed higher CP free water fraction (FWf), increased white matter hyperintensity (WMH) volume, and decreased diffusion tensor image analysis of 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 in controls. The findings suggest that elevated CP FWf may indicate impaired glymphatic function and AD neurodegeneration, potentially serving as a valuable biomarker for AD evaluation and progression.