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

Steward, Anna; Biel, Davina; Brendel, Matthias; Dewenter, Anna; Römer, Sebastian; Rubinski, Anna; Luan, Ying; Dichgans, Martin ; Ewers, Michael und Franzmeier, Nicolai (2022): Functional network segregation is associated with attenuated tau spreading in Alzheimer's disease. In: Alzheimer's & Dementia

Abstract

IntroductionLower 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. MethodsWe 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. ResultsAD 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. DiscussionOur results indicate that tau spreading is facilitated by a more diffusely organized connectome, suggesting that brain network topology modulates tau spreading in AD. HighlightsHigher 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1552-5260
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198