Abstract
INTRODUCTION: Enlargement of the choroidal-ventricular system occurs in aging and Alzheimer's disease (AD), but emerging evidence links these abnormalities to amyloid beta (Aβ) aggregation. We tested this hypothesis by assessing associations between AD pathophysiology and choroidal-ventricular system measures across the AD continuum. METHODS: Ventricular volume, choroid-plexus volume, and ventricular radioactivity after positron emission tomography (PET) tracer injections were analyzed in 385 Translational Biomarkers in Aging and Dementia (TRIAD) and 282 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants using linear models and partial correlations. A composite score combining these measures was also tested against established AD biomarkers. RESULTS: With advancing AD stages, ventricular and choroid-plexus volumes increased while ventricular radioactivity declined. These measures were interrelated, and abnormalities appeared even in amyloid-negative elderly. Across cohorts, they correlated with amyloid- and tau-PET, cerebrospinal fluid (CSF) and plasma p-tau isoforms, glial fibrillary acidic protein (GFAP), and cognition. Voxel-wise analyses showed strong associations with cortical Aβ, mediating downstream tau effects. DISCUSSION: Changes in the choroidal-ventricular system are mutually correlated and carry an additive-effect on cortical Aβ load.