Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia.
connectome
disease epicentre
frontotemporal dementia
gene expression
network spreading
Journal
Brain : a journal of neurology
ISSN: 1460-2156
Titre abrégé: Brain
Pays: England
ID NLM: 0372537
Informations de publication
Date de publication:
05 01 2023
05 01 2023
Historique:
received:
01
09
2021
revised:
14
12
2021
accepted:
30
01
2022
pubmed:
22
2
2022
medline:
11
1
2023
entrez:
21
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35188955
pii: 6533638
doi: 10.1093/brain/awac069
pmc: PMC9825569
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
321-336Subventions
Organisme : Medical Research Council
ID : MR/M023664/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG032306
Pays : United States
Organisme : Medical Research Council
ID : MR/T046015/1
Pays : United Kingdom
Organisme : Fonds de Recherche du Québec-Santé (FRQS)
Organisme : University of California, San Francisco
Organisme : Frontotemporal Lobar Degeneration Neuroimaging Initiative
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : #017-04265
Organisme : Canada Research Chairs Program
Organisme : Medical Research Council
ID : MR/M008525/1
Pays : United Kingdom
Organisme : Fonds de recherche du Québec
Organisme : University of Southern California
Organisme : NIH HHS
ID : R01 AG032306
Pays : United States
Organisme : Medical Research Council
ID : MR/J009482/1
Pays : United Kingdom
Organisme : Fonds de recherche du Québec-Nature et Technologies
Investigateurs
Howard Rosen
(H)
Bradford C Dickerson
(BC)
Kimoko Domoto-Reilly
(K)
David Knopman
(D)
Bradley F Boeve
(BF)
Adam L Boxer
(AL)
John Kornak
(J)
Bruce L Miller
(BL)
William W Seeley
(WW)
Maria-Luisa Gorno-Tempini
(ML)
Scott McGinnis
(S)
Maria Luisa Mandelli
(ML)
Aitana Sogorb Esteve
(AS)
Annabel Nelson
(A)
Arabella Bouzigues
(A)
Carolin Heller
(C)
Caroline V Greaves
(CV)
David Cash
(D)
David L Thomas
(DL)
Emily Todd
(E)
Hanya Benotmane
(H)
Henrik Zetterberg
(H)
Imogen J Swift
(IJ)
Jennifer Nicholas
(J)
Kiran Samra
(K)
Lucy L Russell
(LL)
Martina Bocchetta
(M)
Rachelle Shafei
(R)
Rhian S Convery
(RS)
Carolyn Timberlake
(C)
Thomas Cope
(T)
Timothy Rittman
(T)
Alberto Benussi
(A)
Enrico Premi
(E)
Roberto Gasparotti
(R)
Silvana Archetti
(S)
Stefano Gazzina
(S)
Valentina Cantoni
(V)
Andrea Arighi
(A)
Chiara Fenoglio
(C)
Elio Scarpini
(E)
Giorgio Fumagalli
(G)
Vittoria Borracci
(V)
Giacomina Rossi
(G)
Giorgio Giaccone
(G)
Giuseppe Di Fede
(GD)
Paola Caroppo
(P)
Pietro Tiraboschi
(P)
Sara Prioni
(S)
Veronica Redaelli
(V)
David Tang-Wai
(D)
Ekaterina Rogaeva
(E)
Miguel Castelo-Branco
(M)
Morris Freedman
(M)
Ron Keren
(R)
Sandra Black
(S)
Sara Mitchell
(S)
Christen Shoesmith
(C)
Robart Bartha
(R)
Rosa Rademakers
(R)
Emma van der Ende
(E)
Jackie Poos
(J)
Janne M Papma
(JM)
Lucia Giannini
(L)
Rick van Minkelen
(R)
Yolande Pijnenburg
(Y)
Benedetta Nacmias
(B)
Camilla Ferrari
(C)
Cristina Polito
(C)
Gemma Lombardi
(G)
Valentina Bessi
(V)
Michele Veldsman
(M)
Christin Andersson
(C)
Hakan Thonberg
(H)
Linn Öijerstedt
(L)
Vesna Jelic
(V)
Paul Thompson
(P)
Tobias Langheinrich
(T)
Albert Lladó
(A)
Anna Antonell
(A)
Jaume Olives
(J)
Mircea Balasa
(M)
Nuria Bargalló
(N)
Sergi Borrego-Ecija
(S)
Ana Verdelho
(A)
Carolina Maruta
(C)
Catarina B Ferreira
(CB)
Gabriel Miltenberger
(G)
Frederico Simões do Couto
(FS)
Alazne Gabilondo
(A)
Ana Gorostidi
(A)
Jorge Villanua
(J)
Marta Cañada
(M)
Mikel Tainta
(M)
Miren Zulaica
(M)
Myriam Barandiaran
(M)
Patricia Alves
(P)
Benjamin Bender
(B)
Carlo Wilke
(C)
Lisa Graf
(L)
Annick Vogels
(A)
Mathieu Vandenbulcke
(M)
Philip Van Damme
(P)
Rose Bruffaerts
(R)
Pedro Rosa-Neto
(P)
Serge Gauthier
(S)
Agnès Camuzat
(A)
Alexis Brice
(A)
Anne Bertrand
(A)
Aurélie Funkiewiez
(A)
Daisy Rinaldi
(D)
Dario Saracino
(D)
Olivier Colliot
(O)
Sabrina Sayah
(S)
Catharina Prix
(C)
Elisabeth Wlasich
(E)
Olivia Wagemann
(O)
Sandra Loosli
(S)
Sonja Schönecker
(S)
Tobias Hoegen
(T)
Jolina Lombardi
(J)
Sarah Anderl-Straub
(S)
Adeline Rollin
(A)
Gregory Kuchcinski
(G)
Maxime Bertoux
(M)
Thibaud Lebouvier
(T)
Vincent Deramecourt
(V)
Beatriz Santiago
(B)
Diana Duro
(D)
Maria João Leitão
(MJ)
Maria Rosario Almeida
(MR)
Miguel Tábuas-Pereira
(M)
Sónia Afonso
(S)
Annerose Engel
(A)
Maryna Polyakova
(M)
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.
Références
JAMA Neurol. 2016 Sep 1;73(9):1078-88
pubmed: 27429218
Neuron. 2019 Dec 4;104(5):856-868.e5
pubmed: 31623919
Neuroimage. 2021 Dec 15;245:118703
pubmed: 34736996
Neurobiol Aging. 2022 Mar;111:54-63
pubmed: 34968832
Sci Rep. 2016 Jun 01;6:26782
pubmed: 27245317
Neuroscientist. 2012 Aug;18(4):373-85
pubmed: 21670424
Neuron. 2012 Mar 22;73(6):1216-27
pubmed: 22445348
Nat Neurosci. 2018 Sep;21(9):1251-1259
pubmed: 30082915
Brain. 2013 Oct;136(Pt 10):2979-91
pubmed: 24072486
Neuron. 2012 Mar 22;73(6):1060-2
pubmed: 22445334
Brain. 2011 Sep;134(Pt 9):2456-77
pubmed: 21810890
PLoS One. 2012;7(12):e48121
pubmed: 23272041
J Neurosci. 2016 Jun 22;36(25):6758-70
pubmed: 27335406
Neuroimage. 2000 Jun;11(6 Pt 1):805-21
pubmed: 10860804
Philos Trans R Soc Lond B Biol Sci. 2016 Oct 5;371(1705):
pubmed: 27574314
Nat Rev Neurol. 2017 Jul;13(7):406-419
pubmed: 28621768
Brain. 2020 Jun 1;143(6):1632-1650
pubmed: 32129844
J Neurol Neurosurg Psychiatry. 2018 Apr;89(4):374-381
pubmed: 29101254
Neuroimage. 2018 Feb 15;167:104-120
pubmed: 29155184
J Neurol. 2019 Aug;266(8):2075-2086
pubmed: 31119452
IEEE Trans Med Imaging. 1998 Feb;17(1):87-97
pubmed: 9617910
Front Aging Neurosci. 2018 Mar 06;10:47
pubmed: 29559904
Neuroimage. 2019 Apr 1;189:353-367
pubmed: 30648605
Neurobiol Aging. 2019 Apr;76:71-79
pubmed: 30703628
Neuron. 2012 Mar 22;73(6):1204-15
pubmed: 22445347
Nat Rev Neurol. 2020 Apr;16(4):199-212
pubmed: 32203399
Neurobiol Aging. 2016 Feb;38:176-180
pubmed: 26827655
Acta Neuropathol. 2020 Jan;139(1):27-43
pubmed: 31542807
Acta Neuropathol. 2014 Mar;127(3):423-439
pubmed: 24407427
Biol Psychiatry. 2020 Apr 15;87(8):727-735
pubmed: 31837746
Nature. 2013 Sep 5;501(7465):45-51
pubmed: 24005412
Nat Commun. 2017 Nov 7;8(1):1349
pubmed: 29116093
Neuroimage. 2021 Aug 1;236:118052
pubmed: 33857618
JAMA Neurol. 2020 Jul 1;77(7):829-839
pubmed: 32338734
Ageing Res Rev. 2017 Jul;36:50-63
pubmed: 28315409
J R Soc Interface. 2019 Oct 31;16(159):20190356
pubmed: 31615329
Acta Neuropathol. 2017 Feb;133(2):197-222
pubmed: 28084518
Netw Neurosci. 2019 Mar 01;3(2):475-496
pubmed: 30984903
Neurobiol Aging. 2018 Feb;62:191-196
pubmed: 29172163
Neuroimage. 2021 Nov 1;241:118417
pubmed: 34298083
Neuroimage. 2018 Sep;178:540-551
pubmed: 29860082
Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16574-9
pubmed: 25368179
Nat Rev Neurosci. 2015 Mar;16(3):159-72
pubmed: 25697159
Neuroimage. 2020 Oct 15;220:117038
pubmed: 32585343
Neuroimage Clin. 2018 Jan 31;18:456-466
pubmed: 29868450
Neuroimage. 2018 Oct 1;179:40-50
pubmed: 29894824
Nature. 2012 Sep 20;489(7416):391-399
pubmed: 22996553
JAMA Neurol. 2014 Dec;71(12):1562-6
pubmed: 25317628
Int Rev Psychiatry. 2013 Apr;25(2):130-7
pubmed: 23611343
PLoS Biol. 2019 Nov 21;17(11):e3000495
pubmed: 31751329
J Comput Assist Tomogr. 1994 Mar-Apr;18(2):192-205
pubmed: 8126267
Cold Spring Harb Perspect Biol. 2017 Aug 1;9(8):
pubmed: 28289062
Neuroimage. 2006 Jul 1;31(3):968-80
pubmed: 16530430
Neuroimage. 2013 Nov 15;82:393-402
pubmed: 23719155
Nat Rev Neurol. 2012 Aug;8(8):423-34
pubmed: 22732773
Neuroimage. 2017 May 15;152:60-77
pubmed: 28257929
Elife. 2021 Nov 16;10:
pubmed: 34783653
NMR Biomed. 2019 Apr;32(4):e3752
pubmed: 28654718
Proc Natl Acad Sci U S A. 2018 May 22;115(21):E4880-E4889
pubmed: 29739890
Neuroimage Clin. 2019;24:102079
pubmed: 31795051
Elife. 2015 Sep 07;4:
pubmed: 26344547
Ann Neurol. 2020 May;87(5):725-738
pubmed: 32072667
Trends Neurosci. 2013 Oct;36(10):561-9
pubmed: 23876425
Neuroimage. 2018 Apr 15;170:249-256
pubmed: 28040542
Neuroimage. 2019 May 1;191:81-92
pubmed: 30739059
Brain. 2022 Jun 3;145(5):1805-1817
pubmed: 34633446
Brain. 2010 May;133(Pt 5):1352-67
pubmed: 20410145
Neuroimage Clin. 2017 Apr 26;15:171-180
pubmed: 28529873
Cereb Cortex. 2018 Jul 1;28(7):2655-2664
pubmed: 29722805
Alzheimers Dement. 2020 Jan;16(1):22-36
pubmed: 31636026
Hum Brain Mapp. 1998;6(5-6):348-57
pubmed: 9788071
Cereb Cortex. 2016 Apr;26(4):1843
pubmed: 26796215
Med Image Anal. 2008 Feb;12(1):26-41
pubmed: 17659998
Trends Cogn Sci. 2020 Apr;24(4):302-315
pubmed: 32160567
Proc Natl Acad Sci U S A. 2016 Feb 2;113(5):1435-40
pubmed: 26772314
Neuroimage. 2018 Jul 1;174:191-200
pubmed: 29548850
Lancet Neurol. 2015 Mar;14(3):253-62
pubmed: 25662776
Alzheimers Dement. 2020 Jan;16(1):71-78
pubmed: 31914219
Cell. 2011 Oct 28;147(3):498-508
pubmed: 22036560
Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Sep;3(9):788-797
pubmed: 30170711
J Neurosci Methods. 2012 Jan 30;203(2):386-97
pubmed: 22001222
Brain Connect. 2021 Dec;11(10):799-814
pubmed: 33858198
Proc Natl Acad Sci U S A. 2019 Oct 15;116(42):21219-21227
pubmed: 31570622
J Neurochem. 2016 Aug;138 Suppl 1:54-70
pubmed: 27306735
Nat Neurosci. 2015 Nov;18(11):1546-55
pubmed: 26505566
Neurology. 2002 Jun 11;58(11):1615-21
pubmed: 12058088
Netw Neurosci. 2021 Apr 27;5(2):358-372
pubmed: 34189369
Neuroimage. 2021 Jul 15;235:118008
pubmed: 33789134
Neuroimage. 2019 Jan 15;185:1-11
pubmed: 30317017
Front Neurol. 2018 Feb 02;9:37
pubmed: 29456521
J Neurophysiol. 2011 Sep;106(3):1125-65
pubmed: 21653723
IEEE Trans Med Imaging. 2008 Apr;27(4):425-41
pubmed: 18390341
Neuroimage. 2016 Jan 1;124(Pt A):762-769
pubmed: 25869856
Neuron. 2015 Jun 17;86(6):1518-29
pubmed: 26087168
Cereb Cortex. 2018 Jan 1;28(1):281-294
pubmed: 29088339