Title :

Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study.

Author(s) :

Premi, E. [Auteur]
Pengo, M. [Auteur]
Mattioli, I. [Auteur]
Cantoni, V. [Auteur]
Dukart, J. [Auteur]
Gasparotti, R. [Auteur]
Buratti, E. [Auteur]
Padovani, A. [Auteur]
Bocchetta, M. [Auteur]
Todd, E. G. [Auteur]
Bouzigues, A. [Auteur]
Cash, D. M. [Auteur]
Convery, R. S. [Auteur]
Russell, L. L. [Auteur]
Foster, P. [Auteur]
Thomas, D. L. [Auteur]
Van Swieten, J. C. [Auteur]
Jiskoot, L. C. [Auteur]
Seelaar, H. [Auteur]
Galimberti, D. [Auteur]
Sanchez-Valle, R. [Auteur]
Laforce, R. [Auteur]
Moreno, F. [Auteur]
Synofzik, M. [Auteur]
Graff, C. [Auteur]
Masellis, M. [Auteur]
Tartaglia, M. C. [Auteur]
Rowe, J. B. [Auteur]
Tsvetanov, K. A. [Auteur]
Vandenberghe, R. [Auteur]
Finger, E. [Auteur]
Tiraboschi, P. [Auteur]
De Mendonça, A. [Auteur]
Santana, I. [Auteur]
Butler, C. R. [Auteur]
Ducharme, S. [Auteur]
Gerhard, A. [Auteur]
Levin, J. [Auteur]
Otto, M. [Auteur]
Sorbi, S. [Auteur]
Le Ber, I. [Auteur]
Pasquier, Florence [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Rohrer, J. D. [Auteur]
Borroni, Barbara [Auteur]
Università degli Studi di Brescia = University of Brescia [UniBs]

Journal title :

Neurobiol Dis

Abbreviated title :

Neurobiol Dis

Volume number :

79

Pages :

106068

Publisher :

Elsevier

Publication date :

2023-03-12

ISSN :

1095-953X

Keyword(s) :

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

English keyword(s) :

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

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Submission date :

2024-01-15T23:27:22Z
2024-11-13T10:29:59Z