{"doi":"10.1002/alz.12867","title":"Functional network segregation is associated with attenuated tau spreading in Alzheimer's disease","abstract":"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.","journal":"Alzheimer s & Dementia","year":2022,"id":241918,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":813066,"name":"Davina Biel","orcid":"0000-0002-2597-1992","position":1,"is_corresponding":false},{"id":65410,"name":"Matthias Brendel","orcid":"0000-0002-9247-2843","position":2,"is_corresponding":false},{"id":253513,"name":"Anna Dewenter","orcid":"0000-0002-5636-196X","position":3,"is_corresponding":false},{"id":871512,"name":"Sebastian Niclas Roemer","orcid":"0000-0003-3423-457X","position":4,"is_corresponding":false},{"id":232092,"name":"Anna Rubinski","orcid":"0000-0002-1768-1231","position":5,"is_corresponding":false},{"id":249999,"name":"Ying Luan","orcid":"0000-0003-3403-2353","position":6,"is_corresponding":false},{"id":12191,"name":"Martin Dichgans","orcid":"0000-0002-0654-387X","position":7,"is_corresponding":false},{"id":67599,"name":"Michael Ewers","orcid":"0000-0001-5231-1714","position":8,"is_corresponding":false},{"id":84338,"name":"Nicolai Franzmeier","orcid":"0000-0001-9736-2283","position":9,"is_corresponding":false},{"id":872123,"name":"for the Alzheimer's Disease Neuroimaging Initiative (ADNI)","orcid":null,"position":10,"is_corresponding":false},{"id":871511,"name":"Anna Steward","orcid":"0000-0002-8438-3760","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T00:23:00.865267Z","pmid":"36433865","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}