NeuroImage: Clinical (Jan 2017)
White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort
- Carole H. Sudre,
- Martina Bocchetta,
- David Cash,
- David L. Thomas,
- Ione Woollacott,
- Katrina M. Dick,
- John van Swieten,
- Barbara Borroni,
- Daniela Galimberti,
- Mario Masellis,
- Maria Carmela Tartaglia,
- James B. Rowe,
- Caroline Graff,
- Fabrizio Tagliavini,
- Giovanni Frisoni,
- Robert Laforce, Jr,
- Elizabeth Finger,
- Alexandre de Mendonça,
- Sandro Sorbi,
- Sébastien Ourselin,
- M. Jorge Cardoso,
- Jonathan D. Rohrer,
- Christin Andersson,
- Silvana Archetti,
- Andrea Arighi,
- Luisa Benussi,
- Giuliano Binetti,
- Sandra Black,
- Maura Cosseddu,
- Marie Fallström,
- Carlos Ferreira,
- Chiara Fenoglio,
- Nick C. Fox,
- Morris Freedman,
- Giorgio Fumagalli,
- Stefano Gazzina,
- Roberta Ghidoni,
- Marina Grisoli,
- Vesna Jelic,
- Lize Jiskoot,
- Ron Keren,
- Gemma Lombardi,
- Carolina Maruta,
- Simon Mead,
- Lieke Meeter,
- Rick van Minkelen,
- Benedetta Nacmias,
- Linn Öijerstedt,
- Alessandro Padovani,
- Jessica Panman,
- Michela Pievani,
- Cristina Polito,
- Enrico Premi,
- Sara Prioni,
- Rosa Rademakers,
- Veronica Redaelli,
- Ekaterina Rogaeva,
- Giacomina Rossi,
- Martin N. Rossor,
- Elio Scarpini,
- David Tang-Wai,
- Hakan Thonberg,
- Pietro Tiraboschi,
- Ana Verdelho,
- Jason D. Warren
Affiliations
- Carole H. Sudre
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; Centre for Medical Image Computing, University College London, UK
- Martina Bocchetta
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK
- David Cash
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; Centre for Medical Image Computing, University College London, UK
- David L. Thomas
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; Centre for Medical Image Computing, University College London, UK
- Ione Woollacott
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK
- Katrina M. Dick
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK
- John van Swieten
- Erasmus Medical Center, Rotterdam, Netherlands
- Barbara Borroni
- University of Brescia, Italy
- Daniela Galimberti
- Dept. of Pathophysiology and Transplantation, “Dino Ferrari” Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
- Mario Masellis
- Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute; Department of Medicine, University of Toronto, Canada
- Maria Carmela Tartaglia
- Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Canada
- James B. Rowe
- University of Cambridge, UK
- Caroline Graff
- Karolinska Institutet, Stockholm, Sweden; Karolinska Institutet, Department NVS, Center for Alzheimer Research, Division of Neurogeriatrics, Sweden; Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden
- Fabrizio Tagliavini
- Istituto Neurologico Carlo Besta, Milan, Italy
- Giovanni Frisoni
- IRCCS San Giovanni di Dio Fatebenefratelli Brescia, Italy
- Robert Laforce, Jr
- Université Laval, Quebec, Canada
- Elizabeth Finger
- University of Western Ontario, Ontario, Canada
- Alexandre de Mendonça
- Faculdade de Medicina, Universidade de Lisboa, Portugal
- Sandro Sorbi
- Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy; IRCCS Don Gnocchi, Firenze, Italy
- Sébastien Ourselin
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; Centre for Medical Image Computing, University College London, UK
- M. Jorge Cardoso
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; Centre for Medical Image Computing, University College London, UK
- Jonathan D. Rohrer
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; Corresponding author at: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, WC1N 3BG, London.
- Christin Andersson
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Silvana Archetti
- Biotechnology Laboratory, Department of Diagnostics, Civic Hospital of Brescia, Brescia, Italy
- Andrea Arighi
- Neurology Unit, Department of Physiopathology and Transplantation, Fondazione Cà Granda, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico, Milan, Italy
- Luisa Benussi
- Istituto di Ricovero e Cura a Carattere Scientifico Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
- Giuliano Binetti
- Istituto di Ricovero e Cura a Carattere Scientifico Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
- Sandra Black
- LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, Canada
- Maura Cosseddu
- Centre of Brain Aging, University of Brescia, Brescia, Italy
- Marie Fallström
- Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden
- Carlos Ferreira
- Instituto Ciências Nucleares Aplicadas à Saúde, Universidade de Coimbra, Coimbra, Portugal
- Chiara Fenoglio
- Department of Pathophysiology and Transplantation, ''Dino Ferrari'' Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
- Nick C. Fox
- Dementia Research Centre, UCL Institute of Neurology, UK
- Morris Freedman
- Division of Neurology, Baycrest Centre for Geriatric Care, University of Toronto, Canada
- Giorgio Fumagalli
- Neurology Unit, Fondazione Cà Granda, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico, Milan, Italy; Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
- Stefano Gazzina
- Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Roberta Ghidoni
- Istituto di Ricovero e Cura a Carattere Scientifico Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
- Marina Grisoli
- Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milano, Italy
- Vesna Jelic
- Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden
- Lize Jiskoot
- Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
- Ron Keren
- University Health Network Memory Clinic, Toronto Western Hospital, Toronto, Canada
- Gemma Lombardi
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
- Carolina Maruta
- Lisbon Faculty of Medicine, Language Research Laboratory, Lisbon, Portugal
- Simon Mead
- MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK
- Lieke Meeter
- Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
- Rick van Minkelen
- Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, Netherlands
- Benedetta Nacmias
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
- Linn Öijerstedt
- Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden
- Alessandro Padovani
- Neurology Unit, Department of Medical and Experimental Sciences, University of Brescia, Brescia, Italy
- Jessica Panman
- Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
- Michela Pievani
- Istituto di Ricovero e Cura a Carattere Scientifico Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
- Cristina Polito
- Department of Clinical Pathophysiology, University of Florence, Florence, Italy
- Enrico Premi
- Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy
- Sara Prioni
- Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
- Rosa Rademakers
- Department of Neurosciences, Mayo Clinic, Jacksonville, Florida
- Veronica Redaelli
- Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
- Ekaterina Rogaeva
- Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Canada
- Giacomina Rossi
- Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
- Martin N. Rossor
- Dementia Research Centre, UCL Institute of Neurology, UK
- Elio Scarpini
- Neurology Unit, Department of Physiopathology and Transplantation, Fondazione Cà Granda, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico, Milan, Italy
- David Tang-Wai
- University Health Network Memory Clinic, Toronto Western Hospital, Toronto, Canada
- Hakan Thonberg
- Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden;
- Pietro Tiraboschi
- Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
- Ana Verdelho
- Department of Neurosciences, Santa Maria Hospital, University of Lisbon, Portugal
- Jason D. Warren
- Dementia Research Centre, UCL Institute of Neurology, UK
- Journal volume & issue
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Vol. 15
pp. 171 – 180
Abstract
Genetic frontotemporal dementia is most commonly caused by mutations in the progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. Previous small studies have reported the presence of cerebral white matter hyperintensities (WMH) in genetic FTD but this has not been systematically studied across the different mutations. In this study WMH were assessed in 180 participants from the Genetic FTD Initiative (GENFI) with 3D T1- and T2-weighed magnetic resonance images: 43 symptomatic (7 GRN, 13 MAPT and 23 C9orf72), 61 presymptomatic mutation carriers (25 GRN, 8 MAPT and 28 C9orf72) and 76 mutation negative non-carrier family members. An automatic detection and quantification algorithm was developed for determining load, location and appearance of WMH. Significant differences were seen only in the symptomatic GRN group compared with the other groups with no differences in the MAPT or C9orf72 groups: increased global load of WMH was seen, with WMH located in the frontal and occipital lobes more so than the parietal lobes, and nearer to the ventricles rather than juxtacortical. Although no differences were seen in the presymptomatic group as a whole, in the GRN cohort only there was an association of increased WMH volume with expected years from symptom onset. The appearance of the WMH was also different in the GRN group compared with the other groups, with the lesions in the GRN group being more similar to each other. The presence of WMH in those with progranulin deficiency may be related to the known role of progranulin in neuroinflammation, although other roles are also proposed including an effect on blood-brain barrier permeability and the cerebral vasculature. Future studies will be useful to investigate the longitudinal evolution of WMH and their potential use as a biomarker as well as post-mortem studies investigating the histopathological nature of the lesions.
