Shafiei, Golia;
Bazinet, Vincent;
Dadar, Mahsa;
Manera, Ana L;
Collins, D Louis;
Dagher, Alain;
Borroni, Barbara;
... GENetic Frontotemporal dementia Initiative (GENFI), .; + view all
(2022)
Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia.
Brain
10.1093/brain/awac069.
(In press).
Preview |
Text
awac069.pdf - Accepted Version Download (1MB) | Preview |
Abstract
Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioral variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). We first identify distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally- connected neighbors, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicenter of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and antero-medial temporal areas. Finally, we find that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability, providing an explanation as to how heterogenous pathological entities can lead to the same clinical syndrome.
| Type: | Article |
|---|---|
| Title: | Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/brain/awac069 |
| Publisher version: | https://doi.org/10.1093/brain/awac069 |
| Language: | English |
| Additional information: | © The Author(s) 2021. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/). |
| Keywords: | connectome, disease epicentre, frontotemporal dementia, gene expression, network spreading |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10145242 |
Archive Staff Only
 |
View Item |
