Journal Article

DZNE-2026-00735

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Modular brain networks shape amyloid-driven tau spread and cognitive decline.

Hirsch, F. ; Frontzkowski, L. ; Steward, A. ; Roemer-Cassiano, S. N. ; Biel, D. ; Zhu, Z. ; Palleis, C.DZNE* ; Gnoerich, J.Extern* ; Klonowski, M. ; Höglinger, G.DZNE* ; Brendel, M.DZNE* ; Franzmeier, N.

2026
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.71617

Abstract: Alzheimer's disease involves trans-synaptic spread of tau pathology from temporal lobe epicenters, driven by amyloid beta (Aβ) deposition. How modular brain network architecture shapes this process and the ensuing cognitive decline remains incompletely understood. We tested whether the efficiency with which tau epicenters access cross-network communication pathways modulates Aβ-driven tau propagation.We combined baseline/longitudinal amyloid/tau positron emission tomography (PET) data across two independent AD cohorts (N = 490) with multimodal connectomics data. We quantified epicenter broadcast capacity (EBC), capturing whether tau epicenters preferentially access regions supporting cross-network communication or within-network communication.Higher EBC was associated with faster Aβ-related global tau accumulation, greater spatial tau spread, and steeper cognitive decline. Effects were driven by stronger epicenter communication with cross-network connectors, whereas preferential within-network routing was associated with relative containment of tau spread.We identify a mechanism through which epicenter connectivity biases Aβ-driven tau propagation toward brain-wide broadcast or regional containment, helping explain heterogeneity in disease progression.

Keyword(s): Humans (MeSH) ; tau Proteins: metabolism (MeSH) ; Positron-Emission Tomography (MeSH) ; Cognitive Dysfunction: metabolism (MeSH) ; Cognitive Dysfunction: diagnostic imaging (MeSH) ; Cognitive Dysfunction: pathology (MeSH) ; Brain: metabolism (MeSH) ; Brain: diagnostic imaging (MeSH) ; Brain: pathology (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Female (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Male (MeSH) ; Aged (MeSH) ; Connectome (MeSH) ; Nerve Net: diagnostic imaging (MeSH) ; Nerve Net: metabolism (MeSH) ; Aged, 80 and over (MeSH) ; graph theory ; integration ; neurodegeneration ; neuroimaging ; segregation ; tauopathy ; tau Proteins ; Amyloid beta-Peptides

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))
2. Molecular Neurodegeneration (AG Haass)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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