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dc.contributor.authorShafiei, Golia
dc.contributor.authorBazinet, Vincent
dc.contributor.authorDadar, Mahsa
dc.contributor.authorManera, Ana L
dc.contributor.authorCollins, D Louis
dc.contributor.authorDagher, Alain
dc.contributor.authorBorroni, Barbara
dc.contributor.authorSanchez-Valle, Raquel
dc.contributor.authorMoreno, Fermin
dc.contributor.authorLaforce, Robert
dc.contributor.authorGraff, Caroline
dc.contributor.authorSynofzik, Matthis
dc.contributor.authorGalimberti, Daniela
dc.contributor.authorRowe, James
dc.contributor.authorMasellis, Mario
dc.contributor.authorTartaglia, Maria Carmela
dc.contributor.authorFinger, Elizabeth
dc.contributor.authorVandenberghe, Rik
dc.contributor.authorde Mendonça, Alexandre
dc.contributor.authorTagliavini, Fabrizio
dc.contributor.authorSantana, Isabel
dc.contributor.authorButler, Chris
dc.contributor.authorGerhard, Alex
dc.contributor.authorDanek, Adrian
dc.contributor.authorLevin, Johannes
dc.contributor.authorOtto, Markus
dc.contributor.authorSorbi, Sandro
dc.contributor.authorJiskoot, Lize C
dc.contributor.authorSeelaar, Harro
dc.contributor.authorvan Swieten, John C
dc.contributor.authorRohrer, Jonathan D
dc.contributor.authorMisic, Bratislav
dc.contributor.authorDucharme, Simon
dc.contributor.authorFrontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI)
dc.contributor.authorGENetic Frontotemporal dementia Initiative (GENFI)
dc.date.accessioned2022-04-04T23:30:14Z
dc.date.available2022-04-04T23:30:14Z
dc.date.issued2022-02-21
dc.identifier.issn0006-8950
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/335746
dc.description.abstractConnections 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.
dc.format.mediumPrint-Electronic
dc.publisherOxford University Press (OUP)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectconnectome
dc.subjectdisease epicentre
dc.subjectfrontotemporal dementia
dc.subjectgene expression
dc.subjectnetwork spreading
dc.titleNetwork structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia.
dc.typeArticle
dc.publisher.departmentDepartment of Clinical Neurosciences
dc.date.updated2022-04-01T11:37:29Z
prism.publicationDate2022
prism.publicationNameBrain
dc.identifier.doi10.17863/CAM.83183
dcterms.dateAccepted2022-01-30
rioxxterms.versionofrecord10.1093/brain/awac069
rioxxterms.versionAM
dc.contributor.orcidShafiei, Golia [0000-0002-2036-5571]
dc.contributor.orcidDadar, Mahsa [0000-0003-4008-2672]
dc.contributor.orcidCollins, D Louis [0000-0002-8432-7021]
dc.contributor.orcidDagher, Alain [0000-0002-0945-5779]
dc.contributor.orcidSanchez-Valle, Raquel [0000-0002-2216-1361]
dc.contributor.orcidSynofzik, Matthis [0000-0002-2280-7273]
dc.contributor.orcidRowe, James [0000-0001-7216-8679]
dc.contributor.orcidMasellis, Mario [0000-0002-6244-2096]
dc.contributor.orcidJiskoot, Lize C [0000-0002-8120-7366]
dc.contributor.orcidSeelaar, Harro [0000-0003-1989-7527]
dc.contributor.orcidMisic, Bratislav [0000-0003-0307-2862]
dc.contributor.orcidDucharme, Simon [0000-0002-7309-1113]
dc.identifier.eissn1460-2156
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (103838/Z/14/Z)
pubs.funder-project-idMedical Research Council (MR/J009482/1)
cam.issuedOnline2022-02-21
cam.orpheus.success2022-04-04 - Embargo set during processing via Fast-track
cam.depositDate2022-04-01
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2023-02-21


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Attribution-NonCommercial 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial 4.0 International