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

Hahn L, Eickhoff SB, Mueller K, Schilbach L, Barthel H, Fassbender K, Fliessbach K, Kornhuber J, Prudlo J, Synofzik M, Wiltfang J, Diehl-Schmid J, Otto M, Art JD, Schroeter ML (2024)

Publication Type: Journal article

Publication year: 2024

Journal

eLife eLife Sciences Publications

Book Volume: 13

Article Number: e86085

DOI: 10.7554/eLife.86085

Abstract

Background: 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. Methods: 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 females) and 22 healthy controls (HC) (mean age = 63.6 ± 11.9 years; 13 females). We tested if alterations of fALFF in patients co-localize with the nonpathological distribution of specific neurotransmitter systems and their coding mRNA gene expression. Furthermore, we evaluated if the strength of co-localization is associated with the observed clinical symptoms. Results: Patients displayed significantly reduced fALFF in frontotemporal and frontoparietal regions. These alterations co-localized with the distribution of serotonin (5-HT1b and 5-HT2a) and γ-aminobutyric acid type A (GABAa) receptors, the norepinephrine transporter (NET), and their encoding mRNA gene expression. The strength of co-localization with NET was associated with cognitive symptoms and disease severity of bvFTD. Conclusions: 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. Funding: This study has been supported by the German Consortium for Frontotemporal Lobar Degeneration, funded by the German Federal Ministry of Education and Research (BMBF; grant no. FKZ01GI1007A).

Authors with CRIS profile

Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie

Involved external institutions

Forschungszentrum Jülich / Research Centre Jülich (FZJ) DE Germany (DE) Max-Planck-Institut für Kognitions- und Neurowissenschaften / Max Planck Institute for Human Cognitive and Brain Sciences DE Germany (DE) LVR-Klinikum Düsseldorf DE Germany (DE) Universitätsklinikum Leipzig DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) Technische Universität München (TUM) DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE)

How to cite

APA:

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

MLA:

Hahn, Lisa, et al. "Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems." eLife 13 (2024).

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