Abstract
Cortical tau deposition begins in higher-order association regions and spreads to lower-order primary sensory-motor networks in moderate/advanced Alzheimer's dementia. The neural mechanisms underlying this spatiotemporal pattern remain elusive. Initial evidence has shown that coupled dynamic, low-frequency (<0.1 Hz) brain activity in cerebrospinal fluid (CSF) flow and gray matter (global brain-CSF coupling) might be related to CSF clearance and thus β-amyloid accumulation. Here, we report that tau deposition in higher-order regions, particularly individuals with evaluated β-amyloid, is related to decreased global brain-CSF coupling in humans. Brain dynamics manifesting as propagating waves between higher- and lower-order regions mediate the association between tau and global brain-CSF coupling. Preferential tau deposition in higher-order regions is associated with weaker activation strength there during propagation and less involvement in global brain activity and CSF inflow. The findings suggest an important role of dynamic, spontaneous global brain activity in Alzheimer's tau pathology and cognition.