Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study

Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson’s disease

“…Low correlations are also observed between gene expression and in vivo PET imaging of dopamine transporters 44 . Other works combining unimodal neuroimaging from disease cohorts with PET- and SPECT-derived healthy neurotransmitter receptor and transporter templates have uncovered the co-localization of specific neurotransmitter systems with PD resting state fMRI alterations 45 , dyskinesia- and parkinsonism-associated atrophy in schizophrenia patients 46 , gray matter atrophy in symptomatic FTD and its genetic subtypes 47 , and functional alterations in behavioral variant FTD 48 . Furthermore, our averaged autoradiography-derived receptor templates are correlated with neurobiological processes such as drug-induced cerebral blood flow changes 49 .…”

Frontotemporal dementia patient-derived iPSC neurons show cell pathological hallmarks and evidence for synaptic dysfunction and DNA damage

“…Glutamate-mediated excitotoxicity has been observed in C9-HRE-associated FTD, further underlining the involvement of synaptic perturbations in FTD pathogenesis [12]. Synaptic dysfunction is proposed to occur well before symptom onset and to be a unifying early hallmark in FTD and ALS [21]. In early disease stages, ALS patient motor neurons display altered excitability [24,26].…”

“…Moreover, studies in different cellular and animal models further support the contribution of disturbed glutamatergic and GABAergic neurotransmitter systems in FTD pathogenesis [14, 22–24]. Interestingly, no changes, suggesting alterations in neurotransmitter systems, have been observed in GRN (progranulin) mutation carriers in neuroimaging [21]. However, TDP-43 pathology, which is typically present in GRN mutation carriers, has been suggested to cause disturbances in the dopaminergic system [16].…”

“…Synaptic dysfunction is proposed to occur well before symptom onset and to be a unifying early hallmark in FTD and ALS [21]. In early disease stages, ALS patient motor neurons display altered excitability [24, 26].…”

Functional networks of reward and punishment processing and their molecular profiles predicting the severity of young adult drinking

“…A tool for spatial correlation analyses of MRI data with nuclear imaging derived neurotransmitter maps, JuSpace provides a biologically meaningful framework to this end (Dukart et al, 2021) and offers novel insight into disease mechanisms and associated clinical features (Premi et al, 2023). For instance, in a study of frontotemporal dementia, investigators associated the altered patterns of grey matter volume (GMV) with the distribution of dopamine and acetylcholine pathways in mutation carriers and showed more widespread involvement of dopamine, serotonin, glutamate and acetylcholine pathways in symptomatic individuals (Pengo et al, 2023). Another work focused on a population of unmedicated first-episode schizophrenia and reported GMV alterations in association with the expression of serotonin, dopamine, and gamma amino butyric acid (GABA) receptors and/or transporters (Jingli Chen et al, 2023).…”