title: Neuroimaging Correlates of Frontotemporal Dementia Associated with SQSTM1 Mutations.
abstract: Frontotemporal lobar degeneration (FTLD) is a progressive dementia characterized by focal atrophy of frontal and/or temporal lobes caused by mutations in the gene coding for sequestosome 1 (SQSTM1), among other genes. Rare SQSTM1 gene mutations have been associated with Paget's disease of bone, amyotrophic lateral sclerosis, and, more recently, frontotemporal lobar degeneration (FTLD).
  
  
  
  The aim of the study was to determine whether a characteristic pattern of grey and white matter loss is associated with SQSTM1 dysfunction.
  
  
  
  We performed a voxel-based morphometry (VBM) study in FTD subjects carrying SQSTM1 pathogenic variants (FTD/SQSTM1 mutation carriers; n = 10), compared with FTD subjects not carrying SQSTM1 mutations (Sporadic FTD; n = 20) and healthy controls with no SQSTM1 mutations (HC/SQSTM1 noncarriers; n = 20). The groups were matched according to current age, disease duration, and gender.
  
  
  
  After comparing FTD/SQSTM1 carriers with Sporadic FTD, a predominantly right cortical atrophy pattern was localized in the inferior frontal, medial orbitofrontal, precentral gyri, and the anterior insula. White matter atrophy was found in both medial and inferior frontal gyri, pallidum, and putamen. FTD/SQSTM1 carriers compared with HC/SQSTM1 noncarriers showed atrophy at frontal, temporal, and parietal lobes of both hemispheres whereas the MRI pattern found in Sporadic FTD compared with controls was frontal and left temporal lobe atrophy, extending toward parietal and occipital lobes of both hemispheres.
  
  
  
  These results suggest that fronto-orbito-insular regions including corticospinal projections as described in ALS are probably more susceptible to the damaging effect of SQSTM1 mutations delineatinga specific gene-linked atrophy pattern.
authors.affiliation: Neuroimaging Laboratory, Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|School of Education and Psychology, University of Navarra, Pamplona, Spain.
authors.forename: Elkin
authors.initials: E
authors.lastname: Luis
authors.affiliation: Neuroimaging Laboratory, Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Neuroimaging Laboratory, Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Eudave
authors.affiliation: Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.|CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Ortega-Cubero
authors.affiliation: Centre for Aging Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.|Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: van der Zee
authors.affiliation: Centre for Aging Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gazzina
authors.affiliation: Besta Neurological Institut, Milan, Italy.|Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Universités, Université Pierre et Marie, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Paola
authors.initials: P
authors.lastname: Caroppo
authors.affiliation: Università degli Studi di Torino, Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Rubino
authors.affiliation: Università degli Studi di Torino, Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: D'Agata
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Universités, Université Pierre et Marie, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Ber
authors.affiliation: Neurology Department, Centro Hospitalar e Universitério de Coimbra, Coimbra, Portugal and Faculty of Medicine, Coimbra University, Coimbra, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Santana
authors.affiliation: Neurorradiology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Gil
authors.initials: G
authors.lastname: Cunha
authors.affiliation: Neurogenetics Laboratory, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Almeida
authors.affiliation: Claire Boutoleau-Bretonnière: Department of Neurology, CMRR, Nantes University Hospital, Nantes, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Boutoleau-Bretonnière
authors.affiliation: Department of Genetics, Rouen University Hospital, Rouen, France.|Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|CNR-MAJ, Rouen University Hospital, Rouen, France.|Department of Neurology, Rouen University Hospital, Rouen, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
authors.affiliation: Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|CNR-MAJ, Rouen University Hospital, Rouen, France.
authors.forename: David
authors.initials: D
authors.lastname: Wallon
authors.affiliation: Department of Neuroscience "Rita Levi Montalcini", University of Torino, Turin, Italy.
authors.forename: Innocenzo
authors.initials: I
authors.lastname: Rainero
authors.affiliation: Department of Pathophysiology and Transplantation, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.|Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.affiliation: Neuroimaging Laboratory, Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|School of Education and Psychology, University of Navarra, Pamplona, Spain.|CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain.|Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pastor
authors.affiliation: Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.|CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain.|Memory and Movement Disorders Units, Department of Neurology, University Hospital Mutua de Terrassa, Terrassa, Barcelona, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001921:Brain / Q000000981:diagnostic imaging*; D000073885:C9orf72 Protein / Q000378:metabolism; D005260:Female; D057180:Frontotemporal Dementia / Q000000981:diagnostic imaging* / Q000235:genetics*; D066128:Gray Matter / Q000000981:diagnostic imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D000073216:Mental Status and Dementia Tests; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000071456:Sequestosome-1 Protein / Q000235:genetics*; D013223:Statistics as Topic
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein
keywords: Dementia; SQSTM1 protein; frontotemporal dementia; voxel-based morphometry