TY  - JOUR
AU  - Steward, Anna
AU  - Biel, Davina
AU  - Brendel, Matthias
AU  - Dewenter, Anna
AU  - Roemer, Sebastian
AU  - Rubinski, Anna
AU  - Luan, Ying
AU  - Dichgans, Martin
AU  - Ewers, Michael
AU  - Franzmeier, Nicolai
TI  - Functional network segregation is associated with attenuated tau spreading in Alzheimer's disease.
JO  - Alzheimer's and dementia
VL  - 19
IS  - 5
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2022-01735
SP  - 2034-2046
PY  - 2023
AB  - 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.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.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.Our results indicate that tau spreading is facilitated by a more diffusely organized connectome, suggesting that brain network topology modulates tau spreading in AD.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.
KW  - Humans
KW  - Alzheimer Disease: pathology
KW  - Amyloid beta-Peptides: metabolism
KW  - Brain: pathology
KW  - Cognitive Dysfunction: pathology
KW  - Connectome: methods
KW  - Magnetic Resonance Imaging: methods
KW  - Positron-Emission Tomography
KW  - tau Proteins: metabolism
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Alzheimer's disease (Other)
KW  - functional magnetic resonance imaging (Other)
KW  - network segregation (Other)
KW  - tau positron emission tomography (Other)
KW  - tau spreading (Other)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36433865
DO  - DOI:10.1002/alz.12867
UR  - https://pub.dzne.de/record/165602
ER  -