European journal of nuclear medicine and molecular imaging · 2025
Glucose metabolism alterations and Aβ deposition in AD and FTD are related to the distribution of neurotransmitter systems.
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Bi Sheng, Chen Zhigeng, Li Yixia, Cui Bixiao, Shan Yi, Yang Hongwei, Qi Zhigang, Wu Liyong, Yan Shaozhen, Lu Jie
Аннотация
OBJECTIVE: This study aimed to elucidate the spatial correlations among alterations in glucose metabolism, amyloid-beta (Aβ) deposition, and neurotransmitter systems across Alzheimer's disease (AD), mild cognitive impairment (MCI) and frontotemporal dementia (FTD), while assessing their associations with clinical cognitive decline.
METHODS: In this retrospective cohort study, 507 participants (261 AD, 111 MCI, 62 FTD and 73 normal controls) underwent multimodal neuroimaging, including 18F-FDG PET, 18F-AV45 Aβ PET, and structural MRI. Spatial co-localization of imaging alterations with neurotransmitter receptor/transporter distributions was assessed using the JuSpace toolbox. Spearman correlations evaluated associations between imaging-neurotransmitter co-localization and cognitive scores. False discovery rate (FDR) correction was used to control for P < 0.05 for all analyses.
RESULTS: AD showed glucose hypometabolism in temporoparietal and frontal regions, while FTD was observed in the frontotemporal areas. Spatial co-localization analyses revealed subtype-specific neurotransmitter vulnerabilities: AD glucose hypometabolism correlated with serotonergic, γ-aminobutyric acidergic (GABAergic), dopaminergic, and glutamatergic systems, while FTD correlated with serotonergic, dopaminergic, and opioid receptors. Aβ deposition co-localized with 5HT2a receptor, γ-aminobutyric acid type A (GABAa) receptors, and noradrenaline transporter (NAT) in AD, as well as D1 receptor in MCI. In AD, FDG or Aβ PET-neurotransmitter correlations significantly associated with MMSE/MoCA scores, while Aβ-serotonin transporter (SERT) or Fluorodopa (FDOPA) correlations linked to cognitive decline in Aβ-positive MCI (P < 0.05).
CONCLUSION: This study demonstrates that AD and FTD exhibit unique spatial vulnerabilities in neurotransmitter systems, closely tied to glucose hypometabolism and Aβ pathology. The identification of disease specific neuroimaging-neurotransmitter signatures advances biomarker development and supports targeted therapeutic strategies tailored to molecular pathways.
CLINICAL TRIAL NUMBER: not applicable.
METHODS: In this retrospective cohort study, 507 participants (261 AD, 111 MCI, 62 FTD and 73 normal controls) underwent multimodal neuroimaging, including 18F-FDG PET, 18F-AV45 Aβ PET, and structural MRI. Spatial co-localization of imaging alterations with neurotransmitter receptor/transporter distributions was assessed using the JuSpace toolbox. Spearman correlations evaluated associations between imaging-neurotransmitter co-localization and cognitive scores. False discovery rate (FDR) correction was used to control for P < 0.05 for all analyses.
RESULTS: AD showed glucose hypometabolism in temporoparietal and frontal regions, while FTD was observed in the frontotemporal areas. Spatial co-localization analyses revealed subtype-specific neurotransmitter vulnerabilities: AD glucose hypometabolism correlated with serotonergic, γ-aminobutyric acidergic (GABAergic), dopaminergic, and glutamatergic systems, while FTD correlated with serotonergic, dopaminergic, and opioid receptors. Aβ deposition co-localized with 5HT2a receptor, γ-aminobutyric acid type A (GABAa) receptors, and noradrenaline transporter (NAT) in AD, as well as D1 receptor in MCI. In AD, FDG or Aβ PET-neurotransmitter correlations significantly associated with MMSE/MoCA scores, while Aβ-serotonin transporter (SERT) or Fluorodopa (FDOPA) correlations linked to cognitive decline in Aβ-positive MCI (P < 0.05).
CONCLUSION: This study demonstrates that AD and FTD exhibit unique spatial vulnerabilities in neurotransmitter systems, closely tied to glucose hypometabolism and Aβ pathology. The identification of disease specific neuroimaging-neurotransmitter signatures advances biomarker development and supports targeted therapeutic strategies tailored to molecular pathways.
CLINICAL TRIAL NUMBER: not applicable.