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; 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

doi:10.1016/j.nbd.2023.106068

Journal Articles Neurobiology of Disease Year : 2023

Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study

, , , , , , , , , , , , , , , , , , , , , , , , (1) , , , , , , , , , , , , , , , , (2) , (3) , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , (2) , (2) , (2) , (2) , (2) , (2) , (2) , (2) , , , , , , , , , (3) , (3) , (3) , (3) , (3) , , , , , ,

1
2
3

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

Caroline Graff

Function : Author

Karolinska Institute

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

Isabelle Le Ber

Function : Author

Institut du Cerveau = Paris Brain Institute

Florence Pasquier

Function : Author

Excellence Laboratory LabEx DISTALZ

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

Agnès Camuzat

Function : Author

Institut du Cerveau = Paris Brain Institute

Alexis Brice

Function : Author
PersonId : 1104774
ORCID : 0000-0002-0941-3990
IdRef : 050512935

Institut du Cerveau = Paris Brain Institute

Anne Bertrand

Function : Author

Institut du Cerveau = Paris Brain Institute

Aurélie Funkiewiez

Function : Author

Institut du Cerveau = Paris Brain Institute

Daisy Rinaldi

Function : Author

Institut du Cerveau = Paris Brain Institute

Dario Saracino

Function : Author

Institut du Cerveau = Paris Brain Institute

Olivier Colliot

Function : Author

Institut du Cerveau = Paris Brain Institute

Sabrina Sayah

Function : Author

Institut du Cerveau = Paris Brain Institute

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

Adeline Rollin

Function : Author

Excellence Laboratory LabEx DISTALZ

Gregory Kuchcinski

Function : Author

Excellence Laboratory LabEx DISTALZ

Maxime Bertoux

Function : Author

Excellence Laboratory LabEx DISTALZ

Thibaud Lebouvier

Function : Author
PersonId : 754049
IdHAL : thibaud-lebouvier
ORCID : 0000-0002-6630-394X
IdRef : 177112190

Excellence Laboratory LabEx DISTALZ

Vincent Deramecourt

Function : Author

Excellence Laboratory LabEx DISTALZ

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.

Keywords

Frontotemporal dementia Frontotemporal lobar degeneration Genes Magnetic resonance imaging Positron emission tomography Neurotransmitters Mutatio

Domains

Neurons and Cognition [q-bio.NC] Human genetics

Fichier principal

1-s2.0-S0969996123000827-main.pdf (581.97 Ko)

Origin	Publication funded by an institution
Licence	Attribution

Gestionnaire HAL 8 Sorbonne Université : Connect in order to contact the contributor

https://hal.sorbonne-universite.fr/hal-04523318

Submitted on : Wednesday, March 27, 2024-1:02:36 PM

Last modification on : Thursday, November 7, 2024-2:21:29 PM

Dates and versions

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

Licence

Attribution

Identifiers

HAL Id : hal-04523318 , version 1
DOI : 10.1016/j.nbd.2023.106068
PUBMED : 36898614

Cite

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⟩

Export

BibTeX XML-TEI Dublin Core DC Terms EndNote DataCite

Collections

CNRS ICM SORBONNE-UNIVERSITE SU-MEDECINE ANR

26 View

11 Download

Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study

Abstract

Keywords

Domains

Dates and versions

Licence

Identifiers

Cite

Export

Collections

Altmetric

Share