阿尔茨海默病（AD）和额颞叶痴呆（FTD）中的葡萄糖代谢改变及β淀粉样蛋白（Aβ）沉积与神经递质系统的分布有关。

Glucose metabolism alterations and Aβ deposition in AD and FTD are related to the distribution of neurotransmitter systems.

作者信息

Bi Sheng, Chen Zhigeng, Li Yixia, Cui Bixiao, Shan Yi, Yang Hongwei, Qi Zhigang, Wu Liyong, Yan Shaozhen, Lu Jie

机构信息

Department of Radiology & Nuclear Medicine, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053, China.

Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China.

出版信息

Eur J Nucl Med Mol Imaging. 2025 Aug 7. doi: 10.1007/s00259-025-07485-8.

DOI:10.1007/s00259-025-07485-8

PMID:40773016

Abstract

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 F-FDG PET, F-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.

摘要

目的

本研究旨在阐明阿尔茨海默病（AD）、轻度认知障碍（MCI）和额颞叶痴呆（FTD）患者葡萄糖代谢改变、β-淀粉样蛋白（Aβ）沉积和神经递质系统之间的空间相关性，同时评估它们与临床认知衰退的关联。

方法

在这项回顾性队列研究中，507名参与者（261名AD患者、111名MCI患者、62名FTD患者和73名正常对照）接受了多模态神经成像检查，包括F-FDG PET、F-AV45 Aβ PET和结构MRI。使用JuSpace工具箱评估成像改变与神经递质受体/转运体分布的空间共定位。Spearman相关性分析评估成像-神经递质共定位与认知评分之间的关联。所有分析均采用错误发现率（FDR）校正以控制P<0.05。

结果

AD患者在颞顶叶和额叶区域表现出葡萄糖代谢减低，而FTD患者则出现在额颞叶区域。空间共定位分析揭示了亚型特异性神经递质易损性：AD患者的葡萄糖代谢减低与血清素能、γ-氨基丁酸能（GABA能）、多巴胺能和谷氨酸能系统相关，而FTD患者与血清素能、多巴胺能和阿片受体相关。在AD患者中，Aβ沉积与5HT2a受体、A型γ-氨基丁酸（GABAa）受体和去甲肾上腺素转运体（NAT）共定位，在MCI患者中与D1受体共定位。在AD患者中，FDG或Aβ PET-神经递质相关性与MMSE/MoCA评分显著相关，而Aβ-血清素转运体（SERT）或氟多巴（FDOPA）相关性与Aβ阳性MCI患者的认知衰退相关（P<0.05）。