Structural and diffusion MRI markers of the choroid plexus and perivascular regions are associated with Alzheimer’s disease pathology and cognition

Abstract Background Choroid plexus (ChP) morphology and periventricular diffusion alterations have been implicated in Alzheimer’s disease (AD). However, whether ChP volume and the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index provide complementary glymphatic-related MRI information, and whether their associations with cortical thinning and cognition differ by amyloid-β (Aβ) status, remain unclear. Methods We included 252 participants who were stratified by amyloid PET status: 103 Aβ-positive participants and 149 Aβ-negative participants. ChP volume was quantified using FreeSurfer-based segmentation, and the DTI-ALPS index was derived from diffusion tensor imaging as a periventricular diffusion marker. Plasma Aβ40, Aβ42, p-tau217, and p-tau181 levels, cortical thickness, multidomain cognition, and peak width of skeletonized mean diffusivity (PSMD) were analyzed. Aβ-stratification, interaction, and PSMD-adjusted sensitivity analyses were performed. Results Compared with Aβ-negative participants, Aβ-positive participants had greater ChP volumes and lower DTI-ALPS indices, along with higher plasma p-tau217 and p-tau181 levels and amyloid PET burden and lower plasma Aβ42 levels. ChP volume was negatively associated with the DTI-ALPS index, and this association persisted after additional adjustment for PSMD. Group-specific slopes showed that ChP-cortical thickness associations were more negative and DTI-ALPS-cortical thickness associations were more positive in Aβ-positive than in Aβ-negative participants. In MI-pooled interaction models, Aβ status significantly modified the associations of ChP volume with whole-brain mean cortical thickness (β = -0.371, FDR p = 0.005) and temporal cortical thickness (β = -0.312, FDR p = 0.013). The DTI-ALPS interaction survived FDR correction for temporal cortical thickness (β = 0.273, FDR p = 0.033), but not for whole-brain mean cortical thickness (β = 0.231, FDR p = 0.060). Conclusion ChP volume and the DTI-ALPS index are interrelated but non-identical glymphatic-related MRI phenotypes in the AD continuum. The associations between these parameters and cortical thickness were more evident in Aβ-positive than in Aβ-negative participants and were not fully explained by global white-matter microstructural injury.