Related Experiment Video
Updated: Jul 10, 2026

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Modular brain networks shape amyloid-driven tau spread and cognitive decline
Fabian Hirsch1, Lukas Frontzkowski1,2, Anna Steward1
1Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
Introduction:
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.
Methods:
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.
Results:
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.
Discussion:
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.
Related Concept Videos
Alzheimer Disease ll: Pathophysiology
Dementia l: Introduction
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Alzheimer Disease l: Introduction

