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@ARTICLE{Hahn:1019454,
      author       = {Hahn, Lisa and Eickhoff, Simon and Mueller, Karsten and
                      Dukart, Jürgen},
      title        = {{R}esting-state alterations in behavioral variant
                      frontotemporal dementia are related to the distribution of
                      monoamine and {GABA} neurotransmitter systems},
      journal      = {eLife},
      volume       = {13},
      issn         = {2050-084X},
      address      = {Cambridge},
      publisher    = {eLife Sciences Publications},
      reportid     = {FZJ-2023-05402},
      pages        = {86085},
      year         = {2024},
      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
                      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).},
      cin          = {INM-7},
      ddc          = {600},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {5251 - Multilevel Brain Organization and Variability
                      (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5251},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {38224473},
      UT           = {WOS:001143124900001},
      doi          = {10.7554/eLife.86085},
      url          = {https://juser.fz-juelich.de/record/1019454},
}