Elevation in network dynamics amplifies amyloid‐dependent tau pathology
INTRODUCTION: The role of brain network dynamics in relation to amyloid beta (Aβ) and tau pathology across Braak stages remains unclear. METHODS: In this cross-sectional study of 216 participants from Translational Biomarkers of Aging and Dementia (TRIAD) cohort, we analyzed resting-state functional magnetic resonance imaging using a multilayer modularity algorithm to assess brain network dynamics across 10 predefined functional networks, stratified by amyloid and tau positron emission tomography biomarkers and Braak stages. RESULTS: Switching rates were significantly elevated in Aβ-positive/tau-positive individuals relative to Aβ-negative/tau-negative individuals, and increased progressively with advancing Braak stages. Elevated switching rates were strongly correlated with Aβ and tau burden in dorsal attention network and sensorimotor network, as well as with cognitive severity. Importantly, the interaction between network switching rate and Aβ burden synergistically contributed to accelerated tau accumulation in Braak stage III to V regions. DISCUSSION: These findings support the framework that increased network switching may amplify Aβ-related tau load and cognitive deterioration in Alzheimer's disease.
Authors
- Chris Hsiao (ORCID: https://orcid.org/0009-0009-2062-3516)
- Jaime Fernández Arias (ORCID: https://orcid.org/0000-0002-6810-5920)
- Tevy Chan (ORCID: https://orcid.org/0009-0001-9134-5949)
- Robert Hopewell (ORCID: https://orcid.org/0000-0002-2478-5872)
- Rong Li (ORCID: https://orcid.org/0000-0002-9277-6599)
- Lin Gan (ORCID: https://orcid.org/0000-0003-2160-5722)
- Yue Wang (ORCID: https://orcid.org/0000-0003-0098-5359)
- Ting Zou (ORCID: https://orcid.org/0000-0003-1747-1426)
- Lydia Trudel (ORCID: https://orcid.org/0009-0002-5593-7717)
- Kely Monica Quispialaya Socualaya
- Delphine Olivia‐Lopez
- Jieying Li
- Tharick A. Pascoal
- Seyyed Ali Hosseini
- Nesrine Rahmouni
- Pedro Rosa‐Neto
- Gleb Bezgin
- Yang Yi
- Joseph Therriault
- Qolamreza R. Razlighi
- Arthur C. Macedo
- Jean‐Paul Soucy
- Etienne Aumont
- Serge Gauthier
- Maxime Montembeault
- Yansheng Zheng
- Paolo Vitali
- Brandon J. Hall
Institutions
- Montreal Neurological Institute and Hospital (CA)
- University of Electronic Science and Technology of China (CN)
- University of Pittsburgh (US)
- Cornell University (US)
- Douglas Mental Health University Institute (CA)
- Imaging, Brain, and Neuropsychiatry (FR)
- Southwestern Medical Center (US)
- Sichuan Provincial Hospital of Traditional Chinese Medicine (CN)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1002/alz.71354
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Alzheimer's Association
- Fondation Brain Canada
- Weston Brain Institute
- Consortium canadien en neurodégénérescence associée au vieillissement
- National Natural Science Foundation of China
- National Science and Technology Major Project
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec - Santé