Disease-related cortical thinning in presymptomatic granulin mutation carriers

Sergi Borrego-Écija, Roser Sala-Llonch, John van Swieten, Barbara Borroni, Fermín Moreno, Mario Masellis, Carmela Tartaglia, Caroline Graff, Daniela Galimberti, Robert Laforce, James B. Rowe, Elizabeth Finger, Rik Vandenberghe, Fabrizio Tagliavini, Alexandre de Mendonça, Isabel Santana, Matthis Synofzik, Simon Ducharme, Johannes Levin, Adrian DanekAlex Gerhard, Markus Otto, Chris Butler, Giovanni Frisoni, Sandro Sorbi, Carolin Heller, Martina Bocchetta, David M. Cash, Rhian S. Convery, Katrina M. Moore, Jonathan D. Rohrer, Raquel Sanchez-Valle, Martin N. Rossor, Nick C. Fox, Ione O.C. Woollacott, Rachelle Shafei, Caroline Greaves, Mollie Neason, Rita Guerreiro, Jose Bras, David L. Thomas, Jennifer Nicholas, Simon Mead, Lieke Meeter, Jessica Panman, Janne Papma, Rick van Minkelen, Yolande Pijnenburg, Begoña Indakoetxea, Alazne Gabilondo, Mikel TaintaMD, Maria de Arriba, Ana Gorostidi, Miren Zulaica, Jorge Villanua, Zigor Diaz, Jaume Olives, Albert Lladó, Mircea Balasa, Anna Antonell, Nuria Bargallo, Enrico Premi, Maura Cosseddu, Stefano Gazzina, Alessandro Padovani, Roberto Gasparotti, Silvana Archetti, Sandra Black, Sara Mitchell, Ekaterina Rogaeva, Morris Freedman, Ron Keren, David Tang-Wai, Linn Öijerstedt, Christin Andersson, Vesna Jelic, Hakan Thonberg, Andrea Arighi, Chiara Fenoglio, Elio Scarpini MD, Giorgio Fumagalli, Thomas Cope, Carolyn Timberlake, Timothy Rittman, Christen Shoesmith, Robart Bartha, Rosa Rademakers, Carlo Wilke, Benjamin Bender, Rose Bruffaerts, Philip Vandamme, Mathieu Vandenbulcke, Carolina Maruta, Catarina B. Ferreira, Gabriel Miltenberger, Ana Verdelho, Sónia Afonso, Ricardo Taipa, Paola Caroppo, Giuseppe Di Fede, Giorgio Giaccone, Sara Prioni, Veronica Redaelli, Giacomina Rossi, Pietro Tiraboschi, Diana Duro, Maria Rosario Almeida, Miguel Castelo-Branco, Maria João Leitão, Miguel Tabuas-Pereira, Beatriz Santiago, Serge Gauthier, Pedro Rosa-Neto, Michele Veldsman, Toby Flanagan, Catharina Prix, Tobias Hoegen, Elisabeth Wlasich, Sandra Loosli, Sonja Schonecker, Elisa Semler, Sarah Anderl-Straub

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number102540
JournalNeuroImage: Clinical
Volume29
DOIs
StatePublished - Jan 2021

Keywords

  • Cortical thickness
  • Frontotemporal dementia
  • GRN
  • Genetic mutations
  • Presymptomatic

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

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