Related Experiment Video
Updated: Jun 11, 2026
04:41
Preparation of Oligomeric β-amyloid1-42 and Induction of Synaptic Plasticity Impairment on Hippocampal Slices
Published on: July 14, 2010
Decreased amyloid-related structure-function coupling in preclinical Alzheimer's disease.
Prithvi Arunachalam1,2, Leonard Pieperhoff3,4, Luigi Lorenzini3,5
1Department of Radiology and Nuclear Medicine, UMC Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. p.arunachalam@amsterdamumc.nl.
Communications Medicine
|June 9, 2026
Summary
Early Alzheimer's disease involves brain structure-function decoupling, particularly in visual areas, linked to network changes and compensatory mechanisms. This decoupling may be a biomarker for early detection and prevention trials.
Area of Science:
- Neuroscience
- Neuroimaging
- Alzheimer's Disease Research
Background:
- Brain structural pathways are crucial for functional communication.
- Disruptions in preclinical Alzheimer's disease (AD) may indicate network vulnerability or compensation.
- The impact of early amyloid-beta (Aβ) on structure-function alignment, network organization, cognition, and underlying biological processes in AD is not fully understood.
Purpose of the Study:
- To investigate how early amyloid-beta burden affects brain structure-function coupling (SFC).
- To determine if functional network organization mediates the relationship between Aβ and SFC.
- To explore the role of SFC in mediating the link between Aβ and cognitive function.
- To identify transcriptomic factors influencing Aβ-related SFC.
Main Methods:
- Utilized functional MRI, diffusion MRI, and amyloid-beta PET in 460 non-demented older adults.
- Quantified structure-function coupling using the structural-decoupling index (SDI) globally, by sub-network, and regionally.
- Employed linear models for Aβ burden effects on SDI and mediation analyses for network topology, cognition, and gene expression.
Main Results:
- Amyloid-positive individuals showed higher global SDI, mainly in visual cortices.
- Aβ-associated SDI changes were explained by reduced local clustering, suggesting less segregated processing.
- Elevated SDI in visual regions partially offset the negative cognitive impact of Aβ burden.
- Aβ-related SDI changes correlated with genes involved in Aβ metabolism, microglial activation, and synaptic remodeling.
Conclusions:
- Early Aβ pathology is linked to brain structure-function decoupling, especially in visual cortices, mediated by network changes and molecular factors.
- Reduced structure-function coupling may act as a compensatory mechanism in preclinical AD.
- SDI shows potential as a biomarker for patient stratification and monitoring in AD prevention trials.
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