Disease-related cortical thinning in presymptomatic granulin mutation carriers


Sergi Borrego-Écija, Hospital Clinic Barcelona
Roser Sala-Llonch, Universitat de Barcelona
John van Swieten, Erasmus MC
Barbara Borroni, Università degli Studi di Brescia
Fermín Moreno, Osakidetza, Donostia University Hospital
Mario Masellis, University of Toronto
Carmela Tartaglia, Tanz Centre for Research in Neurodegenerative Diseases
Caroline Graff, Karolinska Universitetssjukhuset
Daniela Galimberti, Università degli Studi di Milano
Robert Laforce, Université Laval
James B. Rowe, MRC Cognition and Brain Sciences Unit
Elizabeth Finger, The University of Western Ontario
Rik Vandenberghe, KU Leuven
Fabrizio Tagliavini, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan
Alexandre de Mendonça, Universidade de Lisboa
Isabel Santana, Universidade de Coimbra, Faculdade de Medicina
Matthis Synofzik, Hertie-Institut für klinische Hirnforschung
Simon Ducharme, Centre Universitaire de Santé McGill
Johannes Levin, Ludwig-Maximilians-Universität München
Adrian Danek, Ludwig-Maximilians-Universität München
Alex Gerhard, Faculty of Biology, Medicine and Health
Markus Otto, Universität Ulm
Chris Butler, University of Oxford
Giovanni Frisoni, IRCCS Centro San Giovanni di Dio Fatebenefratelli
Sandro Sorbi, Università degli Studi di Firenze
Carolin Heller, UCL Queen Square Institute of Neurology
Martina Bocchetta, UCL Queen Square Institute of Neurology
David M. Cash, UCL Queen Square Institute of Neurology
Rhian S. Convery, UCL Queen Square Institute of Neurology
Katrina M. Moore, UCL Queen Square Institute of Neurology
Jonathan D. Rohrer, UCL Queen Square Institute of Neurology
Raquel Sanchez-Valle, Hospital Clinic Barcelona

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NeuroImage: Clinical



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Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an increased CTh loss associated with age and estimated proximity to symptoms onset in GRN carriers, even before the disease onset.

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