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000164077 1001_ $$00000-0002-2036-5571$$aShafiei, Golia$$b0
000164077 245__ $$aNetwork structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia
000164077 260__ $$aOxford$$bOxford Univ. Press$$c2022
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000164077 520__ $$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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000164077 650_7 $$2Other$$aconnectome
000164077 650_7 $$2Other$$adisease epicentre
000164077 650_7 $$2Other$$afrontotemporal dementia
000164077 650_7 $$2Other$$agene expression
000164077 650_7 $$2Other$$anetwork spreading
000164077 650_2 $$2MeSH$$aHumans
000164077 650_2 $$2MeSH$$aFrontotemporal Dementia: diagnostic imaging
000164077 650_2 $$2MeSH$$aFrontotemporal Dementia: genetics
000164077 650_2 $$2MeSH$$aFrontotemporal Dementia: pathology
000164077 650_2 $$2MeSH$$aTranscriptome
000164077 650_2 $$2MeSH$$aBrain: pathology
000164077 650_2 $$2MeSH$$aPick Disease of the Brain: pathology
000164077 650_2 $$2MeSH$$aAtrophy: pathology
000164077 650_2 $$2MeSH$$aConnectome
000164077 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000164077 650_2 $$2MeSH$$aNeuropsychological Tests
000164077 7001_ $$aBazinet, Vincent$$b1
000164077 7001_ $$00000-0003-4008-2672$$aDadar, Mahsa$$b2
000164077 7001_ $$aManera, Ana L$$b3
000164077 7001_ $$00000-0002-8432-7021$$aCollins, D Louis$$b4
000164077 7001_ $$00000-0002-0945-5779$$aDagher, Alain$$b5
000164077 7001_ $$aBorroni, Barbara$$b6
000164077 7001_ $$00000-0002-2216-1361$$aSanchez-Valle, Raquel$$b7
000164077 7001_ $$aMoreno, Fermin$$b8
000164077 7001_ $$aLaforce, Robert$$b9
000164077 7001_ $$aGraff, Caroline$$b10
000164077 7001_ $$0P:(DE-2719)2811275$$aSynofzik, Matthis$$b11$$udzne
000164077 7001_ $$aGalimberti, Daniela$$b12
000164077 7001_ $$aRowe, James B$$b13
000164077 7001_ $$00000-0002-6244-2096$$aMasellis, Mario$$b14
000164077 7001_ $$aTartaglia, Maria Carmela$$b15
000164077 7001_ $$aFinger, Elizabeth$$b16
000164077 7001_ $$aVandenberghe, Rik$$b17
000164077 7001_ $$ade Mendonça, Alexandre$$b18
000164077 7001_ $$aTagliavini, Fabrizio$$b19
000164077 7001_ $$aSantana, Isabel$$b20
000164077 7001_ $$aButler, Chris$$b21
000164077 7001_ $$aGerhard, Alex$$b22
000164077 7001_ $$0P:(DE-2719)2810712$$aDanek, Adrian$$b23$$udzne
000164077 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b24$$udzne
000164077 7001_ $$aOtto, Markus$$b25
000164077 7001_ $$aSorbi, Sandro$$b26
000164077 7001_ $$00000-0002-8120-7366$$aJiskoot, Lize C$$b27
000164077 7001_ $$00000-0003-1989-7527$$aSeelaar, Harro$$b28
000164077 7001_ $$avan Swieten, John C$$b29
000164077 7001_ $$aRohrer, Jonathan D$$b30
000164077 7001_ $$00000-0003-0307-2862$$aMisic, Bratislav$$b31
000164077 7001_ $$00000-0002-7309-1113$$aDucharme, Simon$$b32
000164077 7001_ $$aInitiative, Frontotemporal Lobar Degeneration Neuroimaging$$b33$$eCollaboration Author
000164077 7001_ $$aInitiative, GENetic Frontotemporal dementia$$b34$$eCollaboration Author
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