TY  - CONF
AU  - Hirsch, Fabian
AU  - Frontzkowski, Lukas
AU  - Roemer-Cassiano, Sebastian
AU  - Dehsarvi, Amir
AU  - Steward, Anna
AU  - Dewenter, Anna
AU  - Biel, Davina
AU  - Klonowksi, Madleen
AU  - Zhu, Zeyu
AU  - Gnoerich, Johannes
AU  - Schöll, Michael
AU  - Höglinger, Günter U
AU  - Brendel, Matthias
AU  - Franzmeier, Nicolai
TI  - Connector Hubs Accelerate the Spread of Tau Pathology in Alzheimer's Disease
JO  - Alzheimer's and dementia
VL  - 21
IS  - Suppl 8
SN  - 1552-5260
M1  - DZNE-2025-01505
SP  - e109933
PY  - 2025
AB  - 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
T2  - Alzheimer’s Association International Conference
CY  - 27 Jul 2025 - 31 Jul 2025, Toronto (Canada)
Y2  - 27 Jul 2025 - 31 Jul 2025
M2  - Toronto, Canada
KW  - Humans
KW  - Alzheimer Disease: diagnostic imaging
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: pathology
KW  - tau Proteins: metabolism
KW  - Positron-Emission Tomography
KW  - Brain: diagnostic imaging
KW  - Brain: metabolism
KW  - Brain: pathology
KW  - Male
KW  - Female
KW  - Aged
KW  - Cognitive Dysfunction: diagnostic imaging
KW  - Cognitive Dysfunction: metabolism
KW  - Neuroimaging
KW  - Longitudinal Studies
KW  - Aged, 80 and over
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)1 ; PUB:(DE-HGF)16
C6  - pmid:41433910
C2  - pmc:PMC12724848
DO  - DOI:10.1002/alz70862_109933
UR  - https://pub.dzne.de/record/283098
ER  -