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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>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 \u00b1 10.0 years; 14 females) and 22 healthy controls (HC) (mean age = 63.6 \u00b1 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>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 \u03b3-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.86085","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T05:15:14Z","timestamp":1702876514000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.86085","source":"Crossref","is-referenced-by-count":7,"title":["Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0167-3947","authenticated-orcid":true,"given":"Lisa","family":"Hahn","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02nv7yv05","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre J\u00fclich","place":["J\u00fclich, Germany"]},{"id":[{"id":"https:\/\/ror.org\/024z2rq82","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute 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