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Título: | Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia | Autor: | Shafiei, Golia Bazinet, Vincent Dadar, Mahsa Manera, Ana L. Collins, D. Louis Dagher, Alain Borroni, Barbara Sánchez-Valle, Raquel Moreno, Fermin Laforce, Robert Graff, Caroline Synofzik, Matthis Galimberti, Daniela Rowe, James B. Masellis, Mario Tartaglia, Maria Carmela Finger, Elizabeth Vandenberghe, Rik de Mendonça, Alexandre Tagliavini, Fabrizio Santana, Isabel Butler, Chris Gerhard, Alex Danek, Adrian Levin, Johannes Otto, Markus Sorbi, Sandro Jiskoot, Lize C. Seelaar, Harro van Swieten, John C. Rohrer, Jonathan D. Misic, Bratislav Ducharme, Simon |
Palavras-chave: | connectome; frontotemporal dementia; disease epicentre; gene expression; network spreading | Data: | 5-Jan-2023 | Editora: | Oxford University Press | Projeto: | This research was undertaken thanks in part to funding from the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives initiative. B.M. acknowledges support from the Natural Sciences and Engineering Research Council of Canada (NSERC Discovery Grant RGPIN #017-04265) and from the Canada Research Chairs Program. S.D. receives salary support from the Fonds de Recherche du Québec— Santé (FRQS). G.S. acknowledges support from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Fonds de recherche du Québec—Nature et Technologies (FRQNT). V.B. acknowledges support from the Fonds de recherche du Québec—Nature et Technologies (FRQNT). FTLDNI data collection and sharing was funded by the Frontotemporal Lobar Degeneration Neuroimaging Initiative (National Institutes of Health Grant R01 AG032306) and is coordinated through the University of California, San Francisco, Memory and Aging Center. | Título da revista, periódico, livro ou evento: | Brain | Volume: | 146 | Número: | 1 | Resumo: | 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. | URI: | https://hdl.handle.net/10316/114472 | ISSN: | 0006-8950 1460-2156 |
DOI: | 10.1093/brain/awac069 | Direitos: | openAccess |
Aparece nas coleções: | FMUC Medicina - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia.pdf | 1.23 MB | Adobe PDF | Ver/Abrir |
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