TY  - JOUR
AU  - Hahn, Lisa
AU  - Eickhoff, Simon
AU  - Mueller, Karsten
AU  - Dukart, Jürgen
TI  - Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems
JO  - eLife
VL  - 13
SN  - 2050-084X
CY  - Cambridge
PB  - eLife Sciences Publications
M1  - FZJ-2023-05402
SP  - 86085
PY  - 2024
AB  - 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).
LB  - PUB:(DE-HGF)16
C6  - 38224473
UR  - <Go to ISI:>//WOS:001143124900001
DO  - DOI:10.7554/eLife.86085
UR  - https://juser.fz-juelich.de/record/1019454
ER  -