Functional network contributions to longitudinal tau spread in Posterior Cortical Atrophy.

Abstract

In this study, we investigated longitudinal tau spreading in 23 amyloid-positive individuals with early-stage posterior cortical atrophy (PCA), a clinical syndrome typically characterized by progressive visual cognitive deficits emerging largely from underlying Alzheimer's disease-related tau deposition in posterior cortical areas. Each PCA participant underwent structural MRI and ¹⁸F-Flortaucipir PET at baseline and follow-up (mean interval between baseline and follow-up PET = 1.17 ± 0.29 years). Using directional regression analysis (i.e., a regression-based model testing temporal directionality in tau spread), we quantified how tau epicenters (top 10% regions by baseline tau) predicted longitudinal tau accumulation. Seed-based analysis revealed evidence supporting the role of posterior cortical epicenters in the visual and dorsal attention networks (DAN), showing directional spreading of tau to anterior DAN nodes and the default mode network (DMN), with the largest effects in anterior DAN regions. Complementary graph theory analysis identified the visual network and posterior DMN as hubs of tau spread. These findings collectively suggest that longitudinal tau spread in PCA follows hierarchical progression from primary epicenters within the visual network and DAN to secondary epicenters, including the posterior DMN, possibly mediated by dynamic connectivity reorganization as primary epicenters become saturated with tau pathology.