TY  - JOUR
AU  - Shafiei, Golia
AU  - Bazinet, Vincent
AU  - Dadar, Mahsa
AU  - Manera, Ana L
AU  - Collins, D Louis
AU  - Dagher, Alain
AU  - Borroni, Barbara
AU  - Sanchez-Valle, Raquel
AU  - Moreno, Fermin
AU  - Laforce, Robert
AU  - Graff, Caroline
AU  - Synofzik, Matthis
AU  - Galimberti, Daniela
AU  - Rowe, James B
AU  - Masellis, Mario
AU  - Tartaglia, Maria Carmela
AU  - Finger, Elizabeth
AU  - Vandenberghe, Rik
AU  - de Mendonça, Alexandre
AU  - Tagliavini, Fabrizio
AU  - Santana, Isabel
AU  - Butler, Chris
AU  - Gerhard, Alex
AU  - Danek, Adrian
AU  - Levin, Johannes
AU  - Otto, Markus
AU  - Sorbi, Sandro
AU  - Jiskoot, Lize C
AU  - Seelaar, Harro
AU  - van Swieten, John C
AU  - Rohrer, Jonathan D
AU  - Misic, Bratislav
AU  - Ducharme, Simon
TI  - Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia
JO  - Brain
VL  - 146
IS  - 1
SN  - 0006-8950
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DZNE-2022-00740
SP  - 321-336
PY  - 2022
AB  -  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.
KW  - Humans
KW  - Frontotemporal Dementia: diagnostic imaging
KW  - Frontotemporal Dementia: genetics
KW  - Frontotemporal Dementia: pathology
KW  - Transcriptome
KW  - Brain: pathology
KW  - Pick Disease of the Brain: pathology
KW  - Atrophy: pathology
KW  - Connectome
KW  - Magnetic Resonance Imaging
KW  - Neuropsychological Tests
KW  - connectome (Other)
KW  - disease epicentre (Other)
KW  - frontotemporal dementia (Other)
KW  - gene expression (Other)
KW  - network spreading (Other)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC9825569
C6  - pmid:35188955
DO  - DOI:10.1093/brain/awac069
UR  - https://pub.dzne.de/record/164077
ER  -