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DOI: 10.1055/s-0039-1683479
Graph theoretical analysis of tau burden and the functional connectome in Alzheimers disease
Publication History
Publication Date:
27 March 2019 (online)
Ziel/Aim:
The accumulation of intraneuronal “tau-tangles” is a hallmark of Alzheimer's Disease (AD). The similarity of the distribution of AD-pathology with the anatomy of brain networks has raised questions on the pathways and mechanisms of pathology across the brain. Our objective is to address this question using a graph theoretical analysis approach of the functional connectome and in-vivo measures of tau burden.
Methodik/Methods:
20 AD patients underwent PET imaging using 18F-AV1451 at the Department for Nuclear Medicine, University Hospital Cologne to examine tau tangle distribution, and additionally underwent a functional and structural imaging sequence at the Research Center Juelich. A graphical model of brain network connectivity was constructed for every subject with approximately 600 brain regions serving as nodes and functional connectivity as edges. We use graph theoretical measures to reveal the relationship between tau burden and network characteristics.
Ergebnisse/Results:
To investigate whether highly interconnected 'hub' regions are more likely to receive tau burden, we performed analyses simular to (1) on a node-wise level. A positive relationship between weighted degree and tau pathology showed that connectivity was associated with increased tau pathology. The analysis of participation coefficients did not identify connector nodes to be the driver of this relationship. Furthermore, we examined the differences in network architecture of healthy controls and AD patients and relationships to tau pathology by deviation analyses. We observed significantly lower weighted degrees and higher participation coefficients for AD patients, but only a slight correlation with tau pathology.
Schlussfolgerungen/Conclusions:
A trans-neural spread mechanism of tau pathology is supported by our results of the node-wise approach. The deviation analysis indicates changes of network architecture in AD. AD-related Tau deposition explains some variance, but possibly additive effects of multiple aspects of AD-pathology need to be further investigated.
Literatur/References:
[1] Cope TE, Rittman T, Borchert R. "Tau burden and the functional connectome in Alzheimer's disease and progressive supranuclear palsy." Brain, Feb 1;141(2):550 – 567. doi: 10.1093/brain/awx347.
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