Objective This study aimed to elucidate the spatial correlations among alterations in glucose metabolism, amyloid-beta (A beta) 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 F-18-FDG PET, F-18-AV45 A beta 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, gamma-aminobutyric acidergic (GABAergic), dopaminergic, and glutamatergic systems, while FTD correlated with serotonergic, dopaminergic, and opioid receptors. A beta deposition co-localized with 5HT2a receptor, gamma-aminobutyric acid type A (GABAa) receptors, and noradrenaline transporter (NAT) in AD, as well as D1 receptor in MCI. In AD, FDG or A beta PET-neurotransmitter correlations significantly associated with MMSE/MoCA scores, while A beta-serotonin transporter (SERT) or Fluorodopa (FDOPA) correlations linked to cognitive decline in A beta-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 A beta pathology. The identification of disease specific neuroimaging-neurotransmitter signatures advances biomarker development and supports targeted therapeutic strategies tailored to molecular pathways.
基金：
National Natural Science Foundation of China [82102010, 82394434, 62333002]
第一作者机构：[1]Capital Med Univ, Xuanwu Hosp, Dept Radiol & Nucl Med, 45 Changchun St, Beijing 100053, Peoples R China[2]Beijing Key Lab Magnet Resonance Imaging & Brain I, Beijing, Peoples R China[3]Minist Educ, Key Lab Neurodegenerat Dis, Beijing, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Capital Med Univ, Xuanwu Hosp, Dept Radiol & Nucl Med, 45 Changchun St, Beijing 100053, Peoples R China[2]Beijing Key Lab Magnet Resonance Imaging & Brain I, Beijing, Peoples R China[3]Minist Educ, Key Lab Neurodegenerat Dis, Beijing, Peoples R China
推荐引用方式(GB/T 7714)：
Bi Sheng,Chen Zhigeng,Li Yixia,et al.Glucose metabolism alterations and Aβ deposition in AD and FTD are related to the distribution of neurotransmitter systems[J].EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING.2025,doi:10.1007/s00259-025-07485-8.
APA：
Bi, Sheng,Chen, Zhigeng,Li, Yixia,Cui, Bixiao,Shan, Yi...&Lu, Jie.(2025).Glucose metabolism alterations and Aβ deposition in AD and FTD are related to the distribution of neurotransmitter systems.EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,,
MLA：
Bi, Sheng,et al."Glucose metabolism alterations and Aβ deposition in AD and FTD are related to the distribution of neurotransmitter systems".EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING .(2025)
医学