Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia

作者：Golia Shafiei, Vincent Bazinet, Mahsa Dadar, Ana L. Manera, D. Louis Collins, Alain Dagher, Barbara Borroni, Raquel Sánchez‐Valle, Fermín Moreno, Robert Laforce, Caroline Graff, Matthis Synofzik, Daniela Galimberti, James B. Rowe, Mario Masellis, Maria Carmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, Alexandre de Mendonça, Fabrizio Tagliavini, Isabel Santana, Christopher Butler, Alexander Gerhard, Adrian Danek, Johannes Levin, Markus Otto, Sandro Sorbi, Lize C Jiskoot, Harro Seelaar, John C. van Swieten, Jonathan D. Rohrer, Bratislav Mišić, Simon Ducharme, Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI), Howard Rosen, Bradford C. Dickerson, Kimoko Domoto-Reilly, David S. Knopman, Bradley F. Boeve, Adam L. Boxer, John Kornak, Bruce L. Miller, William W. Seeley, Maria‐Luisa Gorno‐Tempini, Scott McGinnis, Maria Luisa Mandelli, GENetic Frontotemporal dementia Initiative (GENFI), Aitana Sogorb‐Esteve, Annabel Nelson, Arabella Bouzigues, Carolin Heller, Caroline Greaves, David M. Cash, David L. Thomas, Emily Todd, Hanya Benotmane, Henrik Zetterberg, Imogen J. Swift, Jennifer Nicholas, Kiran Samra, Lucy L. Russell, Martina Bocchetta, Rachelle Shafei, Rhian S. Convery, Carolyn Timberlake, Thomas Cope, Timothy Rittman, Alberto Benussi, Enrico Premi, Roberto Gasparotti, Silvana Archetti, Stefano Gazzina, Valentina Cantoni, Andrea Arighi, Chiara Fenoglio, Elio Scarpini, Giorgio Fumagalli, Vittoria Borracci, Giacomina Rossi, Giorgio Giaccone, Giuseppe Di Fede, Paola Caroppo, Pietro Tiraboschi, Sara Prioni, Veronica Redaelli, David F. Tang‐Wai, Ekaterina Rogaeva, Miguel Castelo‐Branco, Morris Freedman, Ron Keren, Sandra E. Black, Sara Mitchell, Christen Shoesmith, Robart Bartha, Rosa Rademakers, Emma van der Ende, Jackie M. Poos, Janne M. Papma, Lucia Giannini, Rick van Minkelen, Yolande A.L. Pijnenburg, Benedetta Nacmias, Camilla Ferrari, Cristina Polito, Gemma Lombardi, Valentina Bessi, Michele Veldsman, Christin Andersson, Håkan Thonberg, Linn Öijerstedt, Vesna Jelić, Paul Thompson, Tobias Langheinrich, Albert Lladó, Anna Antonell, Jaume Olives, Mircea Balasa, Núria Bargalló, Sergi Borrego‐Écija, Ana Verdelho, Carolina Maruta, Catarina B. Ferreira, Gabriel Miltenberger, Frederico Simões do Couto, Alazne Gabilondo, Ana Gorostidi, Jorge Villanúa, Marta Cañada, Mikel Tainta, Miren Zulaica, Myriam Barandiarán, Patricia Alves, Benjamin Bender, Carlo Wilke, Lisa Graf, Annick Vogels, Mathieu Vandenbulcke, Philip Van Damme, Rose Bruffaerts, Pedro Rosa‐Neto, Serge Gauthier, Agnès Camuzat, Alexis Brice, Anne Bertrand, Aurélie Funkiewiez, Daisy Rinaldi, Dario Saracino, Olivier Colliot, Sabrina Sayah, Catharina Prix, Elisabeth Wlasich, Olivia Wagemann, Sandra Loosli, Sonja Schönecker, Tobias Hoegen, Jolina Lombardi, Sarah Anderl‐Straub, Adeline Rollin, Grégory Kuchcinski, Maxime Bertoux, Thibaud Lebouvier, Vincent Deramecourt, Beatriz Santiago, Diana Duro, Maria João Leitão, Maria Rosário Almeida, Miguel Tábuas‐Pereira, Sónia Afonso, Annerose Engel, Maryna Polyakova · 发表于：Brain · 年份：2022 · DOI：10.1093/brain/awac069 · 被引用次数：94 · 研究领域：Functional Brain Connectivity Studies、Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments

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 ...