Home > Publications Database > Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia > print

001     164077
005     20250127111100.0
024 7 _ |a pmc:PMC9825569
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024 7 _ |a 10.1093/brain/awac069
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024 7 _ |a pmid:35188955
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024 7 _ |a 0006-8950
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024 7 _ |a 1460-2156
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037 _ _ |a DZNE-2022-00740
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Shafiei, Golia
|0 0000-0002-2036-5571
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245 _ _ |a Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia
260 _ _ |a Oxford
|c 2022
|b Oxford Univ. Press
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520 _ _ |a Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioural 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). First, we identified 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 neighbours, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicentre of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and antero-medial temporal areas. We found 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.
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650 _ 7 |a connectome
|2 Other
650 _ 7 |a disease epicentre
|2 Other
650 _ 7 |a frontotemporal dementia
|2 Other
650 _ 7 |a gene expression
|2 Other
650 _ 7 |a network spreading
|2 Other
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Frontotemporal Dementia: diagnostic imaging
|2 MeSH
650 _ 2 |a Frontotemporal Dementia: genetics
|2 MeSH
650 _ 2 |a Frontotemporal Dementia: pathology
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Pick Disease of the Brain: pathology
|2 MeSH
650 _ 2 |a Atrophy: pathology
|2 MeSH
650 _ 2 |a Connectome
|2 MeSH
650 _ 2 |a Magnetic Resonance Imaging
|2 MeSH
650 _ 2 |a Neuropsychological Tests
|2 MeSH
700 1 _ |a Bazinet, Vincent
|b 1
700 1 _ |a Dadar, Mahsa
|0 0000-0003-4008-2672
|b 2
700 1 _ |a Manera, Ana L
|b 3
700 1 _ |a Collins, D Louis
|0 0000-0002-8432-7021
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700 1 _ |a Dagher, Alain
|0 0000-0002-0945-5779
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700 1 _ |a Borroni, Barbara
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700 1 _ |a Sanchez-Valle, Raquel
|0 0000-0002-2216-1361
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700 1 _ |a Moreno, Fermin
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700 1 _ |a Laforce, Robert
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700 1 _ |a Graff, Caroline
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700 1 _ |a Synofzik, Matthis
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700 1 _ |a Galimberti, Daniela
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700 1 _ |a Rowe, James B
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700 1 _ |a Masellis, Mario
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700 1 _ |a Tartaglia, Maria Carmela
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700 1 _ |a Finger, Elizabeth
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700 1 _ |a Vandenberghe, Rik
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700 1 _ |a de Mendonça, Alexandre
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700 1 _ |a Tagliavini, Fabrizio
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700 1 _ |a Santana, Isabel
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700 1 _ |a Butler, Chris
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700 1 _ |a Gerhard, Alex
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700 1 _ |a Danek, Adrian
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700 1 _ |a Levin, Johannes
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700 1 _ |a Otto, Markus
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700 1 _ |a Sorbi, Sandro
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700 1 _ |a Jiskoot, Lize C
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700 1 _ |a Seelaar, Harro
|0 0000-0003-1989-7527
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700 1 _ |a van Swieten, John C
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700 1 _ |a Rohrer, Jonathan D
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700 1 _ |a Misic, Bratislav
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700 1 _ |a Ducharme, Simon
|0 0000-0002-7309-1113
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700 1 _ |a Initiative, Frontotemporal Lobar Degeneration Neuroimaging
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700 1 _ |a Initiative, GENetic Frontotemporal dementia
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