%0 Conference Paper
%A Hirsch, Fabian
%A Frontzkowski, Lukas
%A Roemer-Cassiano, Sebastian
%A Dehsarvi, Amir
%A Steward, Anna
%A Dewenter, Anna
%A Biel, Davina
%A Klonowksi, Madleen
%A Zhu, Zeyu
%A Gnoerich, Johannes
%A Schöll, Michael
%A Höglinger, Günter U
%A Brendel, Matthias
%A Franzmeier, Nicolai
%T Connector Hubs Accelerate the Spread of Tau Pathology in Alzheimer's Disease
%J Alzheimer's and dementia
%V 21
%N Suppl 8
%@ 1552-5260
%M DZNE-2025-01505
%P e109933
%D 2025
%X Tau accumulation drives neurodegeneration and cognitive decline in Alzheimer's Disease (AD) and preclinical research suggests that tau spreads transsynaptically across connected neurons. We translated tau spreading models to human neuroimaging data, showing that tau pathology spreads from circumscribed epicenters to connected regions in AD, following the architecture of functional brain networks. To further determine whether the topology of brain networks influences tau spreading dynamics, we investigated whether functional hubs (i.e. regions with strong inter-regional connections) accelerate tau spread in AD. Specifically, we hypothesized that more efficient communication from tau epicenters towards hubs that cross-link large-scale brain networks (connector hubs) rather than hubs that interconnect neighboring regions (local hubs) accelerates amyloid-related tau accumulation and cognitive decline (Figure 1).Longitudinal tau/amyloid-PET and cognitive data from two independent cohorts covering the AD spectrum (ADNI/A4 n = 325/220) were analyzed to examine amyloid-driven spatiotemporal tau accumulation patterns and cognitive decline. Structural- and functional-connectivity templates from healthy controls were used to model the connectional efficiency of subject-level tau epicenters (i.e. 10
%B Alzheimer’s Association International Conference
%C 27 Jul 2025 - 31 Jul 2025, Toronto (Canada)
Y2 27 Jul 2025 - 31 Jul 2025
M2 Toronto, Canada
%K Humans
%K Alzheimer Disease: diagnostic imaging
%K Alzheimer Disease: metabolism
%K Alzheimer Disease: pathology
%K tau Proteins: metabolism
%K Positron-Emission Tomography
%K Brain: diagnostic imaging
%K Brain: metabolism
%K Brain: pathology
%K Male
%K Female
%K Aged
%K Cognitive Dysfunction: diagnostic imaging
%K Cognitive Dysfunction: metabolism
%K Neuroimaging
%K Longitudinal Studies
%K Aged, 80 and over
%K tau Proteins (NLM Chemicals)
%F PUB:(DE-HGF)1 ; PUB:(DE-HGF)16
%9 AbstractJournal Article
%$ pmid:41433910
%2 pmc:PMC12724848
%R 10.1002/alz70862_109933
%U https://pub.dzne.de/record/283098