Functional network segregation is associated with attenuated tau spreading in Alzheimer's disease
Open accessAbstract
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.
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Higher brain network segregation may attenuate cortical tau propagation.
“Higher brain network segregation may also attenuate cortical tau propagation [44].”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [44]
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- Authors
- Steward, A., Biel, D., Brendel, M., Dewenter, A., Roemer, S., Rubinski, A., Luan, Y., Dichgans, M., Ewers, M., Franzmeier, N., & (ADNI), F. T. A. D. N. I.
- Affiliations
- LMU Klinikum (DE)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Franzmeier, Nicolai
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2022-11-25
- Volume
- 19
- Issue
- 5
- Pages
- 2034-2046
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W4310082819
- Cited by
- 39
- References
- 57
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 8 · 2023: 6
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DZNE Pub (submittedVersion, cc-by-nc)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by-nc)
- Funders
- U.S. Department of Defense (U01 AG024904, W81XWH, W81XWH-12-2-, W81XWH-12, W81XWH1220012, AG024904)
- Alzheimer's Association (U01 AG024904, W81XWH-12-2-0012)
- Bristol-Myers Squibb (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Eli Lilly and Company (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Pfizer (AG024904, W81XWH-12-2-0012, U01 AG024904)
- Biogen (W81XWH-12-2-0012, U01 AG024904, AG024904)
- University of Southern California (W81XWH-12-2-0012, U01 AG024904)
- F. Hoffmann-La Roche (W81XWH-12-2-0012, AG024904, U01 AG024904)
- Meso Scale Diagnostics (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Alzheimer's Disease Neuroimaging Initiative (W81XWH-12-2–0012, U01AG024904, AG024904, W81XWH-12-2-)
- BioClinica (U01 AG024904, W81XWH-12-2-0012, AG024904)
- Novartis Pharmaceuticals Corporation (W81XWH-12-2-0012, U01 AG024904, AG024904)
- Northern California Institute for Research and Education (U01 AG024904, W81XWH-12-2-0012)
- Deutsche Forschungsgemeinschaft (EXC 2145, 390857198, 409/193-1 FUGG, INST 409/193‐1 FUGG)
- Eisai (W81XWH-12-2-0012, U01 AG024904, AG024904)
- Servier (AG024904, W81XWH-12-2-0012, U01 AG024904)
- H. Lundbeck A/S (U01 AG024904, AG024904, W81XWH-12-2-0012)
- IXICO (AG024904, W81XWH-12-2-0012, U01 AG024904)
- National Institutes of Health (3u01ag024904-10s2, W81XWH, W81XWH-12-2-0012, U01-AG024904, AG024904)
- Genentech (W81XWH-12-2-0012, AG024904, U01 AG024904)
- Canadian Institutes of Health Research (U01 AG024904, W81XWH-12-2-0012, 390857198)
- National Institute on Aging (U01-AG-024904)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, tau propagation
- MeSH terms
- Alzheimer Disease, Brain, Humans, Magnetic Resonance Imaging, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Cognitive Dysfunction, Connectome
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