Neurobiology of Disease (Apr 2023)
Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study
- Enrico Premi,
- Marta Pengo,
- Irene Mattioli,
- Valentina Cantoni,
- Juergen Dukart,
- Roberto Gasparotti,
- Emanuele Buratti,
- Alessandro Padovani,
- Martina Bocchetta,
- Emily G. Todd,
- Arabella Bouzigues,
- David M. Cash,
- Rhian S. Convery,
- Lucy L. Russell,
- Phoebe Foster,
- David L. Thomas,
- John C. van Swieten,
- Lize C. Jiskoot,
- Harro Seelaar,
- Daniela Galimberti,
- Raquel Sanchez-Valle,
- Robert Laforce, Jr,
- Fermin Moreno,
- Matthis Synofzik,
- Caroline Graff,
- Mario Masellis,
- Maria Carmela Tartaglia,
- James B. Rowe,
- Kamen A. Tsvetanov,
- Rik Vandenberghe,
- Elizabeth Finger,
- Pietro Tiraboschi,
- Alexandre de Mendonça,
- Isabel Santana,
- Chris R. Butler,
- Simon Ducharme,
- Alexander Gerhard,
- Johannes Levin,
- Markus Otto,
- Sandro Sorbi,
- Isabelle Le Ber,
- Florence Pasquier,
- Jonathan D. Rohrer,
- Barbara Borroni,
- Aitana Sogorb Esteve,
- Carolin Heller,
- Caroline V. Greaves,
- Henrik Zetterberg,
- Imogen J. Swift,
- Kiran Samra,
- Rachelle Shafei,
- Carolyn Timberlake,
- Thomas Cope,
- Timothy Rittman,
- Andrea Arighi,
- Chiara Fenoglio,
- Elio Scarpini,
- Giorgio Fumagalli,
- Vittoria Borracci,
- Giacomina Rossi,
- Giorgio Giaccone,
- Giuseppe Di Fede,
- Paola Caroppo,
- Pietro Tiraboschi,
- Sara Prioni,
- Veronica Redaelli,
- David Tang-Wai,
- Ekaterina Rogaeva,
- Miguel Castelo-Branco,
- Morris Freedman,
- Ron Keren,
- Sandra Black,
- Sara Mitchell,
- Christen Shoesmith,
- Robart Bartha,
- Rosa Rademakers,
- Jackie Poos,
- Janne M. Papma,
- Lucia Giannini,
- Rick van Minkelen,
- Yolande Pijnenburg,
- Benedetta Nacmias,
- Camilla Ferrari,
- Cristina Polito,
- Gemma Lombardi,
- Valentina Bessi,
- Michele Veldsman,
- Christin Andersson,
- Hakan Thonberg,
- Linn Öijerstedt,
- Vesna Jelic,
- Paul Thompson,
- Tobias Langheinrich,
- Albert Lladó,
- Anna Antonell,
- Jaume Olives,
- Mircea Balasa,
- Nuria Bargalló,
- Sergi Borrego-Ecija,
- Ana Verdelho,
- Carolina Maruta,
- Catarina B. Ferreira,
- Gabriel Miltenberger,
- Frederico Simões do Couto,
- Alazne Gabilondo,
- Ana Gorostidi,
- Jorge Villanua,
- Marta Cañada,
- Mikel Tainta,
- Miren Zulaica,
- Myriam Barandiaran,
- Patricia Alves,
- Benjamin Bender,
- Carlo Wilke,
- Lisa Graf,
- Annick Vogels,
- Mathieu Vandenbulcke,
- Philip Van Damme,
- Rose Bruffaerts,
- Koen Poesen,
- Pedro Rosa-Neto,
- Serge Gauthier,
- Agnès Camuzat,
- Alexis Brice,
- Anne Bertrand,
- Aurélie Funkiewiez,
- Daisy Rinaldi,
- Dario Saracino,
- Olivier Colliot,
- Sabrina Sayah,
- Catharina Prix,
- Elisabeth Wlasich,
- Olivia Wagemann,
- Sandra Loosli,
- Sonja Schönecker,
- Tobias Hoegen,
- Jolina Lombardi,
- Sarah Anderl-Straub,
- Adeline Rollin,
- Gregory Kuchcinski,
- Maxime Bertoux,
- Thibaud Lebouvier,
- Vincent Deramecourt,
- Beatriz Santiago,
- Diana Duro,
- Maria João Leitão,
- Maria Rosario Almeida,
- Miguel Tábuas-Pereira,
- Sónia Afonso
Affiliations
- Enrico Premi
- Neurology, Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia, Italy
- Marta Pengo
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Irene Mattioli
- Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Valentina Cantoni
- Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Juergen Dukart
- Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research CentreJülich, Jülich, Germany; Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Roberto Gasparotti
- Neuroradiology Unit, Department of Medical and Surgical Specialties, University of Brescia, Brescia, Italy
- Emanuele Buratti
- ICGEB, Trieste, Italy
- Alessandro Padovani
- Neurology, Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia, Italy; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Martina Bocchetta
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Centre for Cognitive and Clinical Neuroscience, Division of Psychology, Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, London, United Kingdom
- Emily G. Todd
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
- Arabella Bouzigues
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
- David M. Cash
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom
- Rhian S. Convery
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
- Lucy L. Russell
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
- Phoebe Foster
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
- David L. Thomas
- Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
- John C. van Swieten
- Department of Neurology and Alzheimer center, Erasmus Medical Center Rotterdam, the Netherlands
- Lize C. Jiskoot
- Department of Neurology and Alzheimer center, Erasmus Medical Center Rotterdam, the Netherlands
- Harro Seelaar
- Department of Neurology and Alzheimer center, Erasmus Medical Center Rotterdam, the Netherlands
- Daniela Galimberti
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
- Raquel Sanchez-Valle
- Neurology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques, Barcelona, Spain
- Robert Laforce, Jr
- Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, Faculté de Médecine, Université Laval, Québec, Canada
- Fermin Moreno
- Hospital Universitario Donostia, San Sebastian, Spain
- Matthis Synofzik
- Division Translational Genomics of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
- Caroline Graff
- Karolinska Institutet, Department NVS, Division of Neurogeriatrics, Stockholm, Sweden; Unit for Hereditray Dementia, Theme Aging, Karolinska University Hospital, Solna, Stockholm, Sweden
- Mario Masellis
- Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, ON, Canada
- Maria Carmela Tartaglia
- Toronto Western Hospital, Tanz Centre for Research in Neurodegenerative Disease, Toronto, ON, Canada
- James B. Rowe
- Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust and Medical Research Council Cognition and brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom
- Kamen A. Tsvetanov
- Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust and Medical Research Council Cognition and brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom
- Rik Vandenberghe
- Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium
- Elizabeth Finger
- Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada
- Pietro Tiraboschi
- Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico Carlo Besta, Milan, Italy
- Alexandre de Mendonça
- Faculty of Medicine, University of Lisbon, Lisbon, Portugal
- Isabel Santana
- Neurology Department, Centro Hospitalar e Universitário de Coimbra, Portugal
- Chris R. Butler
- Department of Clinical Neurology, University of Oxford, Oxford, United Kingdom
- Simon Ducharme
- Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
- Alexander Gerhard
- Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom; Departments of Geriatric Medicine and Nuclear Medicine, University of Duisburg-Essen, Germany
- Johannes Levin
- Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Munich Cluster of System Neurology, Munich, Germany
- Markus Otto
- Department of Neurology, University Hospital Halle, Halle, Germany
- Sandro Sorbi
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy; IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy
- Isabelle Le Ber
- Sorbonne Université, Paris Brain Institute – Institut du Cerveau – ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Centre de référence des démences rares ou précoces, IM2A, Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Reference Network for Rare Neurological Diseases (ERN-RND)
- Florence Pasquier
- University of Lille, France; Inserm 1172, Lille, France; CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France
- Jonathan D. Rohrer
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
- Barbara Borroni
- Neurology, Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia, Italy; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Corresponding author at: Clinica Neurologica, Dipartimento Scienze Cliniche e Sperimentali, Università degli Studi di Brescia, P.le Spedali Civili 1, 25123 Brescia, Italy.
- Aitana Sogorb Esteve
- Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute at University College London, UCL Queen Square Institute of Neurology, London, UK
- Carolin Heller
- Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK
- Caroline V. Greaves
- Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK
- Henrik Zetterberg
- UK Dementia Research Institute at University College London, UCL Queen Square Institute of Neurology, London, UK; Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
- Imogen J. Swift
- Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute at University College London, UCL Queen Square Institute of Neurology, London, UK
- Kiran Samra
- Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK
- Rachelle Shafei
- Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK
- Carolyn Timberlake
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Thomas Cope
- Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK
- Timothy Rittman
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Andrea Arighi
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy
- Chiara Fenoglio
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy
- Elio Scarpini
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy
- Giorgio Fumagalli
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy
- Vittoria Borracci
- Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
- Giacomina Rossi
- Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
- Giorgio Giaccone
- Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
- Giuseppe Di Fede
- Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
- Paola Caroppo
- Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
- Pietro Tiraboschi
- Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
- Sara Prioni
- Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
- Veronica Redaelli
- Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
- David Tang-Wai
- The University Health Network, Krembil Research Institute, Toronto, Canada
- Ekaterina Rogaeva
- Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada
- Miguel Castelo-Branco
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Morris Freedman
- Baycrest Health Sciences, Rotman Research Institute, University of Toronto, Toronto, Canada
- Ron Keren
- The University Health Network, Toronto Rehabilitation Institute, Toronto, Canada
- Sandra Black
- Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada
- Sara Mitchell
- Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada
- Christen Shoesmith
- Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada
- Robart Bartha
- Department of Medical Biophysics, The University of Western Ontario, London, Ontario, Canada; Centre for Functional and Metabolic Mapping, Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada
- Rosa Rademakers
- Center for Molecular Neurology, University of Antwerp
- Jackie Poos
- Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
- Janne M. Papma
- Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
- Lucia Giannini
- Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
- Rick van Minkelen
- Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, Netherlands
- Yolande Pijnenburg
- Amsterdam University Medical Centre, Amsterdam VUmc, Amsterdam, Netherlands
- Benedetta Nacmias
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
- Camilla Ferrari
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
- Cristina Polito
- Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, Nuclear Medicine Unit, University of Florence, Florence, Italy
- Gemma Lombardi
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
- Valentina Bessi
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
- Michele Veldsman
- Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK
- Christin Andersson
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Hakan Thonberg
- Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden
- Linn Öijerstedt
- Center for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Bioclinicum, Karolinska Institutet, Solna, Sweden; Unit for Hereditary Dementias, Theme Aging, Karolinska University Hospital, Solna, Sweden
- Vesna Jelic
- Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden
- Paul Thompson
- Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK
- Tobias Langheinrich
- Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK; Manchester Centre for Clinical Neurosciences, Department of Neurology, Salford Royal NHS Foundation Trust, Manchester, UK
- Albert Lladó
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain
- Anna Antonell
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain
- Jaume Olives
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain
- Mircea Balasa
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain
- Nuria Bargalló
- Imaging Diagnostic Center, Hospital Clínic, Barcelona, Spain
- Sergi Borrego-Ecija
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain
- Ana Verdelho
- Department of Neurosciences and Mental Health, Centro Hospitalar Lisboa Norte - Hospital de Santa Maria & Faculty of Medicine, University of Lisbon, Lisbon, Portugal
- Carolina Maruta
- Laboratory of Language Research, Centro de Estudos Egas Moniz, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
- Catarina B. Ferreira
- Laboratory of Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
- Gabriel Miltenberger
- Faculty of Medicine, University of Lisbon, Lisbon, Portugal
- Frederico Simões do Couto
- Faculdade de Medicina, Universidade Católica Portuguesa, Portugal
- Alazne Gabilondo
- Cognitive Disorders Unit, Department of Neurology, Donostia University Hospital, San Sebastian, Gipuzkoa, Spain; Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain
- Ana Gorostidi
- Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain
- Jorge Villanua
- OSATEK, University of Donostia, San Sebastian, Gipuzkoa, Spain
- Marta Cañada
- CITA Alzheimer, San Sebastian, Gipuzkoa, Spain
- Mikel Tainta
- Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain
- Miren Zulaica
- Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain
- Myriam Barandiaran
- Cognitive Disorders Unit, Department of Neurology, Donostia University Hospital, San Sebastian, Gipuzkoa, Spain; Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain
- Patricia Alves
- Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain; Department of Educational Psychology and Psychobiology, Faculty of Education, International University of La Rioja, Logroño, Spain
- Benjamin Bender
- Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany
- Carlo Wilke
- Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany; Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
- Lisa Graf
- Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany
- Annick Vogels
- Department of Human Genetics, KU Leuven, Leuven, Belgium
- Mathieu Vandenbulcke
- Geriatric Psychiatry Service, University Hospitals Leuven, Belgium; Neuropsychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium
- Philip Van Damme
- Neurology Service, University Hospitals Leuven, Belgium; Laboratory for Neurobiology, VIB-KU Leuven Centre for Brain Research, Leuven, Belgium
- Rose Bruffaerts
- Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Biomedical Research Institute, Hasselt University, 3500 Hasselt, Belgium
- Koen Poesen
- Laboratory for Molecular Neurobiomarker Research, KU Leuven, Leuven, Belgium
- Pedro Rosa-Neto
- Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, Québec, Canada
- Serge Gauthier
- Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, Department of Neurology & Neurosurgery, McGill University, Montreal, Québec, Canada
- Agnès Camuzat
- Sorbonne Université, Paris Brain Institute – Institut du Cerveau – ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France
- Alexis Brice
- Sorbonne Université, Paris Brain Institute – Institut du Cerveau – ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Reference Network for Rare Neurological Diseases (ERN-RND)
- Anne Bertrand
- Sorbonne Université, Paris Brain Institute – Institut du Cerveau – ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Inria, Aramis Project-Team, F-75013 Paris, France; Centre pour l'Acquisition et le Traitement des Images, Institut du Cerveau et la Moelle, Paris, France
- Aurélie Funkiewiez
- Centre de référence des démences rares ou précoces, IM2A, Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France;; Sorbonne Université, Paris Brain Institute – Institut du Cerveau – ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France
- Daisy Rinaldi
- Centre de référence des démences rares ou précoces, IM2A, Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Université, Paris Brain Institute – Institut du Cerveau – ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France
- Dario Saracino
- Sorbonne Université, Paris Brain Institute – Institut du Cerveau – ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Inria, Aramis project-team, F-75013 Paris, France; Centre de référence des démences rares ou précoces, IM2A, Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France
- Olivier Colliot
- Sorbonne Université, Paris Brain Institute – Institut du Cerveau – ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Inria, Aramis project-team, F-75013 Paris, France; Centre pour l'Acquisition et le Traitement des Images, Institut du Cerveau et la Moelle, Paris, France
- Sabrina Sayah
- Sorbonne Université, Paris Brain Institute – Institut du Cerveau – ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France
- Catharina Prix
- Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany
- Elisabeth Wlasich
- Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany
- Olivia Wagemann
- Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany
- Sandra Loosli
- Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany
- Sonja Schönecker
- Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany
- Tobias Hoegen
- Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany
- Jolina Lombardi
- Department of Neurology, University of Ulm, Ulm, Germany
- Sarah Anderl-Straub
- Department of Neurology, University of Ulm, Ulm, Germany
- Adeline Rollin
- CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France
- Gregory Kuchcinski
- Univ Lille, France; Inserm 1172, Lille, France; CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France
- Maxime Bertoux
- Inserm 1172, Lille, France; CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France
- Thibaud Lebouvier
- Univ Lille, France; Inserm 1172, Lille, France; CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France
- Vincent Deramecourt
- Univ Lille, France; Inserm 1172, Lille, France; CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France
- Beatriz Santiago
- Neurology Department, Centro Hospitalar e Universitario de Coimbra, Coimbra, Portugal
- Diana Duro
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Maria João Leitão
- Centre of Neurosciences and Cell Biology, Universidade de Coimbra, Coimbra, Portugal
- Maria Rosario Almeida
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Miguel Tábuas-Pereira
- Neurology Department, Centro Hospitalar e Universitario de Coimbra, Coimbra, Portugal
- Sónia Afonso
- Instituto Ciencias Nucleares Aplicadas a Saude, Universidade de Coimbra, Coimbra, Portugal
- Journal volume & issue
-
Vol. 179
p. 106068
Abstract
Background: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches. Methods: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Magnetic Resonance Imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission.We included 392 mutation carriers (157 GRN, 164 C9orf72, 71 MAPT), together with 276 non-carrier cognitively healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in mutation carriers (relative to HC) are correlated with specific neurotransmitter systems in prodromal (CDR® plus NACC FTLD = 0.5) and in symptomatic (CDR® plus NACC FTLD≥1) FTD. Results: In prodromal stages of C9orf72 disease, voxel-based brain changes were significantly associated with spatial distribution of dopamine and acetylcholine pathways; in prodromal MAPT disease with dopamine and serotonin pathways, while in prodromal GRN disease no significant findings were reported (p < 0.05, Family Wise Error corrected). In symptomatic FTD, a widespread involvement of dopamine, serotonin, glutamate and acetylcholine pathways across all genetic subtypes was found. Social cognition scores, loss of empathy and poor response to emotional cues were found to correlate with the strength of GMV colocalization of dopamine and serotonin pathways (all p < 0.01). Conclusions: This study, indirectly assessing neurotransmitter deficits in monogenic FTD, provides novel insight into disease mechanisms and might suggest potential therapeutic targets to counteract disease-related symptoms.
