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  Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems

Hahn, L., Eickhoff, S. B., Mueller, K., Schilbach, L., Barthel, H., Fassbender, K., et al. (2024). Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems. eLife, 13: e86085. doi:10.7554/eLife.86085.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000C-1034-7 Version Permalink: https://hdl.handle.net/21.11116/0000-000F-1831-F
Genre: Journal Article

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 Creators:
Hahn, Lisa1, 2, Author
Eickhoff, Simon B.1, 2, Author
Mueller, Karsten3, Author           
Schilbach, Leonhard4, 5, Author
Barthel, Henryk6, Author
Fassbender, Klaus7, Author
Fliessbach, Klaus8, 9, Author
Kornhuber, Johannes10, Author
Prudlo, Johannes9, 11, Author
Synofzik, Matthis9, 12, Author
Wiltfang, Jens9, 13, 14, Author
Diehl-Schmid, Janine15, 16, Author
FTLD Consortium, Author              
Otto, Markus17, 18, Author
Dukart, Juergen1, 2, Author
Schroeter, Matthias L.19, 20, Author                 
Affiliations:
1Institute of Neuroscience and Medicine, Research Center Jülich, Germany, ou_persistent22              
2Institute of Systems Neuroscience, University Hospital Düsseldorf, Germany, ou_persistent22              
3Method and Development Group Neural Data Science and Statistical Computing, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_3282987              
4LVR-Klinikum Düsseldorf, Germany, ou_persistent22              
5Medical Faculty, Ludwig Maximilians University Munich, Germany, ou_persistent22              
6Department of Nuclear Medicine, University of Leipzig, Germany, ou_persistent22              
7Department of Neurology, Saarland University Homburg, Germany, ou_persistent22              
8Department of Psychiatry and Psychotherapy, University Bonn, Germany, ou_persistent22              
9German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, ou_persistent22              
10Department of Psychiatry and Psychotherapy, University Clinic Erlangen, Germany, ou_persistent22              
11Department of Neurology, University Medicine Rostock, Germany, ou_persistent22              
12Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Eberhard Karls University Tübingen, Germany, ou_persistent22              
13Department of Psychiatry and Psychotherapy, Georg August University, Göttingen, Germany, ou_persistent22              
14Neurosciences and Signaling Group, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Portugal, ou_persistent22              
15Department of Psychiatry and Psychotherapy, TU Munich, Germany, ou_persistent22              
16kbo-Inn-Salzach-Klinikum, Clinical Center for Psychiatry, Psychotherapy, Psychosomatic Medicine, Geriatrics and Neurology, Wasserburg/Inn, Germany, ou_persistent22              
17Department of Neurology, Ulm University, Germany, ou_persistent22              
18Department of Neurology, Martin Luther University Halle-Wittenberg, Germany, ou_persistent22              
19Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
20Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              

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Free keywords: GABA; Frontotemporal dementia; Human; Medicine; Monoamines; Neurodegeneration; Neuroscience; Resting-state fMRI; Selective vulnerability
 Abstract: Aside to clinical changes, behavioral variant frontotemporal dementia (bvFTD) is characterized by progressive structural and functional alterations in frontal and temporal regions. We examined if there is a selective vulnerability of specific neurotransmitter systems in bvFTD by evaluating the link between disease-related functional alterations and the spatial distribution of specific neurotransmitter systems and their underlying gene expression levels.

Maps of fractional amplitude of low frequency fluctuations (fALFF) were derived as a measure of local activity from resting-state functional magnetic resonance imaging for 52 bvFTD patients (mean age = 61.5 ± 10.0 years; 14 female) and 22 healthy controls (HC) (mean age = 63.6 ± 11.9 years; 13 female). We tested if alterations of fALFF in patients co-localize with the non-pathological distribution of specific neurotransmitter systems and their coding mRNA gene expression. Further, we evaluated if the strength of co-localization is associated with the observed clinical symptoms.

Patients displayed significantly reduced fALFF in fronto-temporal and fronto-parietal regions. These alterations co-localized with the distribution of serotonin (5-HT1b, 5-HT2a), dopamine (D2), and γ-aminobutyric acid (GABAa) receptors, the norepinephrine transporter (NET), and their encoding mRNA gene expression. The strength of co-localization with D2 and NET was associated with cognitive symptoms and disease severity of bvFTD.

Local brain functional activity reductions in bvFTD followed the distribution of specific neurotransmitter systems indicating a selective vulnerability. These findings provide novel insight into the disease mechanisms underlying functional alterations. Our data-driven method opens the road to generate new hypotheses for pharmacological interventions in neurodegenerative diseases even beyond bvFTD.

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Language(s): eng - English
 Dates: 2023-01-102023-12-142024-01-15
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.7554/eLife.86085
PMID: 38224473
PMC: PMC10789488
 Degree: -

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Project name : -
Grant ID : 01GI1007A
Funding program : -
Funding organization : German Federal Ministry of Education and Research (BMBF)
Project name : -
Grant ID : SCHR 774/5-1
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft (DFG)
Project name : -
Grant ID : eHealthSax Initiative
Funding program : -
Funding organization : Sächsische Aufbaubank
Project name : TheVirtualBrain-Cloud
Grant ID : 826421
Funding program : Horizon 2020
Funding organization : European Union
Project name : -
Grant ID : -
Funding program : Neurodegenerative Disease Research (GENFI-prox)
Funding organization : European Union

Source 1

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Title: eLife
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Cambridge : eLife Sciences Publications
Pages: - Volume / Issue: 13 Sequence Number: e86085 Start / End Page: - Identifier: Other: URL
ISSN: 2050-084X
CoNE: https://pure.mpg.de/cone/journals/resource/2050-084X