Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems
© 2024, Hahn et al..
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 non-pathological 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).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
eLife - 13(2024) vom: 15. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hahn, Lisa [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.01.2024 Date Revised 17.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.7554/eLife.86085 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Hahn, Lisa |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems |
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| 500 | |a Date Revised 17.01.2024 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024, Hahn et al. | ||
| 520 | |a 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 | ||
| 520 | |a 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 non-pathological 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a GABA | |
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| 650 | 4 | |a medicine | |
| 650 | 4 | |a monoamines | |
| 650 | 4 | |a neurodegeneration | |
| 650 | 4 | |a neuroscience | |
| 650 | 4 | |a resting-state fMRI | |
| 650 | 4 | |a selective vulnerability | |
| 650 | 7 | |a Amines |2 NLM | |
| 650 | 7 | |a Serotonin |2 NLM | |
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| 650 | 7 | |a Norepinephrine Plasma Membrane Transport Proteins |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a gamma-Aminobutyric Acid |2 NLM | |
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| 700 | 1 | |a Mueller, Karsten |e verfasserin |4 aut | |
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| 700 | 1 | |a Barthel, Henryk |e verfasserin |4 aut | |
| 700 | 1 | |a Fassbender, Klaus |e verfasserin |4 aut | |
| 700 | 1 | |a Fliessbach, Klaus |e verfasserin |4 aut | |
| 700 | 1 | |a Kornhuber, Johannes |e verfasserin |4 aut | |
| 700 | 1 | |a Prudlo, Johannes |e verfasserin |4 aut | |
| 700 | 1 | |a Synofzik, Matthis |e verfasserin |4 aut | |
| 700 | 1 | |a Wiltfang, Jens |e verfasserin |4 aut | |
| 700 | 1 | |a Diehl-Schmid, Janine |e verfasserin |4 aut | |
| 700 | 0 | |a FTLD Consortium |e verfasserin |4 aut | |
| 700 | 1 | |a Otto, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Dukart, Juergen |e verfasserin |4 aut | |
| 700 | 1 | |a Schroeter, Matthias L |e verfasserin |4 aut | |
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