title: Pattern of structural and functional brain abnormalities in asymptomatic granulin mutation carriers.
abstract: BACKGROUND
  To investigate the patterns of brain atrophy, white matter (WM) tract changes, and functional connectivity (FC) abnormalities in asymptomatic granulin (GRN) mutation carriers.
  
  
  METHODS
  Ten cognitively normal subjects (five mutation carriers, GRN+; years to estimated disease onset: 12±7; five mutation noncarriers, GRN-) underwent a clinical and imaging (structural, diffusion tensor, and resting-state functional magnetic resonance imaging) assessment. Brain atrophy was measured with cortical thickness analysis, WM abnormalities with tract-based spatial statistics, and FC with independent component analysis.
  
  
  RESULTS
  GRN+ showed smaller cortical thickness than GRN- in the right orbitofrontal and precentral gyrus and left rostral middle frontal gyrus. WM tracts abnormalities were limited to increased axial diffusivity in the right cingulum, superior longitudinal fasciculus, and corticospinal tract. There were no differences in FC of resting-state networks.
  
  
  CONCLUSIONS
  Brain atrophy and WM tract abnormalities in frontal-parietal circuits can be detected at least a decade before the estimated symptom onset in asymptomatic mutation carriers.
authors.affiliation: Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Pievani
authors.affiliation: Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Paternicò
authors.affiliation: NeuroBioGen Lab-Memory Clinic, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Benussi
authors.affiliation: NeuroBioGen Lab-Memory Clinic, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
authors.affiliation: Neuroradiology and Angiology Unit, Fondazione Poliambulanza, Brescia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orlandini
authors.affiliation: Neuroradiology and Angiology Unit, Fondazione Poliambulanza, Brescia, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Cobelli
authors.affiliation: Neuroradiology and Angiology Unit, Fondazione Poliambulanza, Brescia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Magnaldi
authors.affiliation: Proteomics Unit, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ghidoni
authors.affiliation: Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy; Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland. Electronic address: gfrisoni@fatebenefratelli.it.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
mesh_terms: D000328:Adult; D001284:Atrophy; D001921:Brain / Q000002:abnormalities* / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006579:Heterozygote; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009154:Mutation; D009434:Neural Pathways / Q000002:abnormalities / Q000503:physiopathology; D009929:Organ Size; D000077153:Progranulins; D012146:Rest; D066127:White Matter / Q000002:abnormalities / Q000503:physiopathology
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
keywords: Cortical thickness; Diffusion tensor; FTLD; Magnetic resonance imaging; Progranulin; Resting-state functional MRI