Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study - Sorbonne Université
Journal Articles Neurobiology of Disease Year : 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 , Fermin Moreno , Matthis Synofzik , Caroline Graff (1) , 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 (2) , Florence Pasquier (3) , 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 (2) , Alexis Brice (2) , Anne Bertrand (2) , Aurélie Funkiewiez (2) , Daisy Rinaldi (2) , Dario Saracino (2) , Olivier Colliot (2) , Sabrina Sayah (2) , Catharina Prix , Elisabeth Wlasich , Olivia Wagemann , Sandra Loosli , Sonja Schönecker , Tobias Hoegen , Jolina Lombardi , Sarah Anderl-Straub , Adeline Rollin (3) , Gregory Kuchcinski (3) , Maxime Bertoux (3) , Thibaud Lebouvier (3) , Vincent Deramecourt (3) , Beatriz Santiago , Diana Duro , Maria João Leitão , Maria Rosario Almeida , Miguel Tábuas-Pereira , Sónia Afonso
Enrico Premi
  • Function : Author
Marta Pengo
  • Function : Author
Irene Mattioli
  • Function : Author
Valentina Cantoni
  • Function : Author
Juergen Dukart
  • Function : Author
Roberto Gasparotti
  • Function : Author
Emanuele Buratti
  • Function : Author
Alessandro Padovani
  • Function : Author
Martina Bocchetta
  • Function : Author
Emily G Todd
  • Function : Author
Arabella Bouzigues
  • Function : Author
David M Cash
  • Function : Author
Rhian S Convery
  • Function : Author
Lucy L Russell
  • Function : Author
Phoebe Foster
  • Function : Author
David L Thomas
  • Function : Author
John C van Swieten
  • Function : Author
Lize C Jiskoot
  • Function : Author
Harro Seelaar
  • Function : Author
Daniela Galimberti
  • Function : Author
Raquel Sanchez-Valle
  • Function : Author
Robert Laforce
  • Function : Author
Fermin Moreno
  • Function : Author
Matthis Synofzik
  • Function : Author
Mario Masellis
  • Function : Author
Maria Carmela Tartaglia
  • Function : Author
James B Rowe
  • Function : Author
Kamen A Tsvetanov
  • Function : Author
Rik Vandenberghe
  • Function : Author
Elizabeth Finger
  • Function : Author
Pietro Tiraboschi
  • Function : Author
Alexandre de Mendonça
  • Function : Author
Isabel Santana
  • Function : Author
Chris R Butler
  • Function : Author
Simon Ducharme
  • Function : Author
Alexander Gerhard
  • Function : Author
Johannes Levin
  • Function : Author
Markus Otto
  • Function : Author
Sandro Sorbi
  • Function : Author
Jonathan D Rohrer
  • Function : Author
Barbara Borroni
  • Function : Author
  • PersonId : 1368489
Aitana Sogorb Esteve
  • Function : Author
Carolin Heller
  • Function : Author
Caroline V Greaves
  • Function : Author
Henrik Zetterberg
  • Function : Author
Imogen J Swift
  • Function : Author
Kiran Samra
  • Function : Author
Rachelle Shafei
  • Function : Author
Carolyn Timberlake
  • Function : Author
Thomas Cope
  • Function : Author
Timothy Rittman
  • Function : Author
Andrea Arighi
  • Function : Author
Chiara Fenoglio
  • Function : Author
Elio Scarpini
  • Function : Author
Giorgio Fumagalli
  • Function : Author
Vittoria Borracci
  • Function : Author
Giacomina Rossi
  • Function : Author
Giorgio Giaccone
  • Function : Author
Giuseppe Di Fede
  • Function : Author
Paola Caroppo
  • Function : Author
Pietro Tiraboschi
  • Function : Author
Sara Prioni
  • Function : Author
Veronica Redaelli
  • Function : Author
David Tang-Wai
  • Function : Author
Ekaterina Rogaeva
  • Function : Author
Miguel Castelo-Branco
  • Function : Author
Morris Freedman
  • Function : Author
Ron Keren
  • Function : Author
Sandra Black
  • Function : Author
Sara Mitchell
  • Function : Author
Christen Shoesmith
  • Function : Author
Robart Bartha
  • Function : Author
Rosa Rademakers
  • Function : Author
Jackie Poos
  • Function : Author
Janne M Papma
  • Function : Author
Lucia Giannini
  • Function : Author
Rick van Minkelen
  • Function : Author
Yolande Pijnenburg
  • Function : Author
Benedetta Nacmias
  • Function : Author
Camilla Ferrari
  • Function : Author
Cristina Polito
  • Function : Author
Gemma Lombardi
  • Function : Author
Valentina Bessi
  • Function : Author
Michele Veldsman
  • Function : Author
Christin Andersson
  • Function : Author
Hakan Thonberg
  • Function : Author
Linn Öijerstedt
  • Function : Author
Vesna Jelic
  • Function : Author
Paul Thompson
  • Function : Author
Tobias Langheinrich
  • Function : Author
Albert Lladó
  • Function : Author
Anna Antonell
  • Function : Author
Jaume Olives
  • Function : Author
Mircea Balasa
  • Function : Author
Nuria Bargalló
  • Function : Author
Sergi Borrego-Ecija
  • Function : Author
Ana Verdelho
  • Function : Author
Carolina Maruta
  • Function : Author
Catarina B Ferreira
  • Function : Author
Gabriel Miltenberger
  • Function : Author
Frederico Simões Do Couto
  • Function : Author
Alazne Gabilondo
  • Function : Author
Ana Gorostidi
  • Function : Author
Jorge Villanua
  • Function : Author
Marta Cañada
  • Function : Author
Mikel Tainta
  • Function : Author
Miren Zulaica
  • Function : Author
Myriam Barandiaran
  • Function : Author
Patricia Alves
  • Function : Author
Benjamin Bender
  • Function : Author
Carlo Wilke
  • Function : Author
Lisa Graf
  • Function : Author
Annick Vogels
  • Function : Author
Mathieu Vandenbulcke
  • Function : Author
Philip van Damme
  • Function : Author
Rose Bruffaerts
  • Function : Author
Koen Poesen
  • Function : Author
Pedro Rosa-Neto
  • Function : Author
Serge Gauthier
  • Function : Author
Alexis Brice
Catharina Prix
  • Function : Author
Elisabeth Wlasich
  • Function : Author
Olivia Wagemann
  • Function : Author
Sandra Loosli
  • Function : Author
Sonja Schönecker
  • Function : Author
Tobias Hoegen
  • Function : Author
Jolina Lombardi
  • Function : Author
Sarah Anderl-Straub
  • Function : Author
Thibaud Lebouvier
Beatriz Santiago
  • Function : Author
Diana Duro
  • Function : Author
Maria João Leitão
  • Function : Author
Maria Rosario Almeida
  • Function : Author
Miguel Tábuas-Pereira
  • Function : Author
Sónia Afonso
  • Function : Author

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.
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hal-04523318 , version 1 (27-03-2024)

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Enrico Premi, Marta Pengo, Irene Mattioli, Valentina Cantoni, Juergen Dukart, et al.. Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study. Neurobiology of Disease, 2023, 179, pp.106068. ⟨10.1016/j.nbd.2023.106068⟩. ⟨hal-04523318⟩
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