Functional network segregation is associated with attenuated tau spreading in Alzheimer's disease.

Introduction: Lower network segregation is associated with accelerated cognitive decline in Alzheimer's disease (AD), yet it is unclear whether less segregated brain networks facilitate connectivity-mediated tau spreading.

Methods: We combined resting state functional magnetic resonance imaging (fMRI) with longitudinal tau positron emission tomography (PET) in 42 betamyloid-negative controls and 81 amyloid beta positive individuals across the AD spectrum. Network segregation was determined using resting-state fMRI-assessed connectivity among 400 cortical regions belonging to seven networks.

Results: AD subjects with higher network segregation exhibited slower brain-wide tau accumulation relative to their baseline entorhinal tau PET burden (typical onset site of tau pathology). Second, by identifying patient-specific tau epicenters with highest baseline tau PET we found that stronger epicenter segregation was associated with a slower rate of tau accumulation in the rest of the brain in relation to baseline epicenter tau burden.

Discussion: Our results indicate that tau spreading is facilitated by a more diffusely organized connectome, suggesting that brain network topology modulates tau spreading in AD.

Highlights: Higher brain network segregation is associated with attenuated tau pathology accumulation in Alzheimer's disease (AD). A patient-tailored approach allows for the more precise localization of tau epicenters. The functional segregation of subject-specific tau epicenters predicts the rate of future tau accumulation.