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Early neurotransmitters changes in prodromal frontotemporal dementia
- Source :
- Neurobiology of disease, Neurobiology of Disease, 179:106068. Academic Press, Neurobiology of disease 179, 106068 (2023). doi:10.1016/j.nbd.2023.106068
- Publication Year :
- 2023
-
Abstract
- Crown Copyright © 2023 Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).<br />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.<br />This work is supported by JPND grant “GENFI-prox” (2019–02248), the Centre d'Investigation Clinique (ICM, France) and the Centre pour l'Acquisition et le Traitement des Images platform (CATI, France), the UK Medical Research Council, the Italian Ministry of Health (CoEN015 and Ricerca Corrente), and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant, and the Italian Ministry of Health (GR-2018-12365105). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Alzheimer's Society grant (AS-PG-16-007), and the Bluefield Project. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198).
- Subjects :
- Serotonin
Positron emission tomography
Frontotemporal dementia
Frontotemporal lobar degeneration
Genes
Magnetic resonance imaging
Mutation
Neurotransmitters
C9orf72 Protein
Dopamine
Medizin
tau Proteins
diagnostic imaging [Frontotemporal Dementia]
Acetylcholine
genetics [tau Proteins]
methods [Magnetic Resonance Imaging]
Pick Disease of the Brain
Neurology
ddc:570
Humans
Human medicine
genetics [Frontotemporal Dementia]
genetics [C9orf72 Protein]
Subjects
Details
- Language :
- English
- ISSN :
- 09699961 and 1095953X
- Volume :
- 179
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Disease
- Accession number :
- edsair.doi.dedup.....c90bbde4067ff7fd56c70e1db66b7802