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 Mag-netic 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 (R) plus NACC FTLD = 0.5) and in symptomatic (CDR (R) 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.

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; Sogorb Esteve, Aitana; Heller, Carolin; V Greaves, Caroline; Zetterberg, Henrik; J Swift, Imogen; Samra, Kiran; Shafei, Rachelle; Timberlake, Carolyn; Cope, Thomas; Rittman, Timothy; Arighi, Andrea; Fenoglio, Chiara; Scarpini, Elio; Fumagalli, Giorgio; Borracci, Vittoria; Rossi, Giacomina; Giaccone, Giorgio; Di Fede, Giuseppe; Caroppo, Paola; Tiraboschi, Pietro; Prioni, Sara; Redaelli, Veronica; Tang-Wai, David; Rogaeva, Ekaterina; Castelo-Branco, Miguel; Freedman, Morris; Keren, Ron; Black, Sandra; Mitchell, Sara; Shoesmith, Christen; Bartha, Robart; Rademakers, Rosa; Poos, Jackie; M Papma, Janne; Giannini, Lucia; van Minkelen, Rick; Pijnenburg, Yolande; Nacmias, Benedetta; Ferrari, Camilla; Polito, Cristina; Lombardi, Gemma; Bessi, Valentina; Veldsman, Michele; Andersson, Christin; Thonberg, Hakan; Öijerstedt, Linn; Jelic, Vesna; Thompson, Paul; Langheinrich, Tobias; Lladó, Albert; Antonell, Anna; Olives, Jaume; Balasa, Mircea; Bargalló, Nuria; Borrego-Ecija, Sergi; Verdelho, Ana; Maruta, Carolina; B Ferreira, Catarina; Miltenberger, Gabriel; Simões do Couto, Frederico; Gabilondo, Alazne; Gorostidi, Ana; Villanua, Jorge; Cañada, Marta; Tainta, Mikel; Zulaica, Miren; Barandiaran, Myriam; Alves, Patricia; Bender, Benjamin; Wilke, Carlo; Graf, Lisa; Vogels, Annick; Vandenbulcke, Mathieu; Van Damme, Philip; Bruffaerts, Rose; Poesen, Koen; Rosa-Neto, Pedro; Gauthier, Serge; Camuzat, Agnès; Brice, Alexis; Bertrand, Anne; Funkiewiez, Aurélie; Rinaldi, Daisy; Saracino, Dario; Colliot, Olivier; Sayah, Sabrina; Prix, Catharina; Wlasich, Elisabeth; Wagemann, Olivia; Loosli, Sandra; Schönecker, Sonja; Hoegen, Tobias; Lombardi, Jolina; Anderl-Straub, Sarah; Rollin, Adeline; Kuchcinski, Gregory; Bertoux, Maxime; Lebouvier, Thibaud; Deramecourt, Vincent; Santiago, Beatriz; Duro, Diana; João Leitão, Maria; Rosario Almeida, Maria; Tábuas-Pereira, Miguel; Afonso, Sónia. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - 179:(2023), pp. 1060681-1060689. [10.1016/j.nbd.2023.106068]

Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study

Giorgio Fumagalli;
2023-01-01

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 Mag-netic 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 (R) plus NACC FTLD = 0.5) and in symptomatic (CDR (R) 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.
2023
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; Sogorb Esteve, Aitana; Heller, Carolin; V Greaves, Caroline; Zetterberg, Henrik; J Swift, Imogen; Samra, Kiran; Shafei, Rachelle; Timberlake, Carolyn; Cope, Thomas; Rittman, Timothy; Arighi, Andrea; Fenoglio, Chiara; Scarpini, Elio; Fumagalli, Giorgio; Borracci, Vittoria; Rossi, Giacomina; Giaccone, Giorgio; Di Fede, Giuseppe; Caroppo, Paola; Tiraboschi, Pietro; Prioni, Sara; Redaelli, Veronica; Tang-Wai, David; Rogaeva, Ekaterina; Castelo-Branco, Miguel; Freedman, Morris; Keren, Ron; Black, Sandra; Mitchell, Sara; Shoesmith, Christen; Bartha, Robart; Rademakers, Rosa; Poos, Jackie; M Papma, Janne; Giannini, Lucia; van Minkelen, Rick; Pijnenburg, Yolande; Nacmias, Benedetta; Ferrari, Camilla; Polito, Cristina; Lombardi, Gemma; Bessi, Valentina; Veldsman, Michele; Andersson, Christin; Thonberg, Hakan; Öijerstedt, Linn; Jelic, Vesna; Thompson, Paul; Langheinrich, Tobias; Lladó, Albert; Antonell, Anna; Olives, Jaume; Balasa, Mircea; Bargalló, Nuria; Borrego-Ecija, Sergi; Verdelho, Ana; Maruta, Carolina; B Ferreira, Catarina; Miltenberger, Gabriel; Simões do Couto, Frederico; Gabilondo, Alazne; Gorostidi, Ana; Villanua, Jorge; Cañada, Marta; Tainta, Mikel; Zulaica, Miren; Barandiaran, Myriam; Alves, Patricia; Bender, Benjamin; Wilke, Carlo; Graf, Lisa; Vogels, Annick; Vandenbulcke, Mathieu; Van Damme, Philip; Bruffaerts, Rose; Poesen, Koen; Rosa-Neto, Pedro; Gauthier, Serge; Camuzat, Agnès; Brice, Alexis; Bertrand, Anne; Funkiewiez, Aurélie; Rinaldi, Daisy; Saracino, Dario; Colliot, Olivier; Sayah, Sabrina; Prix, Catharina; Wlasich, Elisabeth; Wagemann, Olivia; Loosli, Sandra; Schönecker, Sonja; Hoegen, Tobias; Lombardi, Jolina; Anderl-Straub, Sarah; Rollin, Adeline; Kuchcinski, Gregory; Bertoux, Maxime; Lebouvier, Thibaud; Deramecourt, Vincent; Santiago, Beatriz; Duro, Diana; João Leitão, Maria; Rosario Almeida, Maria; Tábuas-Pereira, Miguel; Afonso, Sónia
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; Sogorb Esteve, Aitana; Heller, Carolin; V Greaves, Caroline; Zetterberg, Henrik; J Swift, Imogen; Samra, Kiran; Shafei, Rachelle; Timberlake, Carolyn; Cope, Thomas; Rittman, Timothy; Arighi, Andrea; Fenoglio, Chiara; Scarpini, Elio; Fumagalli, Giorgio; Borracci, Vittoria; Rossi, Giacomina; Giaccone, Giorgio; Di Fede, Giuseppe; Caroppo, Paola; Tiraboschi, Pietro; Prioni, Sara; Redaelli, Veronica; Tang-Wai, David; Rogaeva, Ekaterina; Castelo-Branco, Miguel; Freedman, Morris; Keren, Ron; Black, Sandra; Mitchell, Sara; Shoesmith, Christen; Bartha, Robart; Rademakers, Rosa; Poos, Jackie; M Papma, Janne; Giannini, Lucia; van Minkelen, Rick; Pijnenburg, Yolande; Nacmias, Benedetta; Ferrari, Camilla; Polito, Cristina; Lombardi, Gemma; Bessi, Valentina; Veldsman, Michele; Andersson, Christin; Thonberg, Hakan; Öijerstedt, Linn; Jelic, Vesna; Thompson, Paul; Langheinrich, Tobias; Lladó, Albert; Antonell, Anna; Olives, Jaume; Balasa, Mircea; Bargalló, Nuria; Borrego-Ecija, Sergi; Verdelho, Ana; Maruta, Carolina; B Ferreira, Catarina; Miltenberger, Gabriel; Simões do Couto, Frederico; Gabilondo, Alazne; Gorostidi, Ana; Villanua, Jorge; Cañada, Marta; Tainta, Mikel; Zulaica, Miren; Barandiaran, Myriam; Alves, Patricia; Bender, Benjamin; Wilke, Carlo; Graf, Lisa; Vogels, Annick; Vandenbulcke, Mathieu; Van Damme, Philip; Bruffaerts, Rose; Poesen, Koen; Rosa-Neto, Pedro; Gauthier, Serge; Camuzat, Agnès; Brice, Alexis; Bertrand, Anne; Funkiewiez, Aurélie; Rinaldi, Daisy; Saracino, Dario; Colliot, Olivier; Sayah, Sabrina; Prix, Catharina; Wlasich, Elisabeth; Wagemann, Olivia; Loosli, Sandra; Schönecker, Sonja; Hoegen, Tobias; Lombardi, Jolina; Anderl-Straub, Sarah; Rollin, Adeline; Kuchcinski, Gregory; Bertoux, Maxime; Lebouvier, Thibaud; Deramecourt, Vincent; Santiago, Beatriz; Duro, Diana; João Leitão, Maria; Rosario Almeida, Maria; Tábuas-Pereira, Miguel; Afonso, Sónia. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - 179:(2023), pp. 1060681-1060689. [10.1016/j.nbd.2023.106068]
File in questo prodotto:
File Dimensione Formato  
2023 Premi et al.pdf

accesso aperto

Tipologia: Versione editoriale (Publisher’s layout)
Licenza: Creative commons
Dimensione 581.97 kB
Formato Adobe PDF
581.97 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/400460
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact