Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases
Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases
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DOI：
10.1126/scitranslmed.abe5640
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发表时间：
2021-10-13
影响因子：
17.1
通讯作者：
Brendel, Matthias
中科院分区：
文献类型：
--
作者：
Xiang, Xianyuan;Wind, Karin;Brendel, Matthias
2-脱氧-2-[F-18]氟-d-葡萄糖正电子发射断层扫描(FDG-PET)被广泛应用于脑葡萄糖代谢的研究。在这里，我们在小鼠模型和神经退行性疾病患者中调查了FDG-PET信号是否直接受到小胶质细胞葡萄糖摄取的影响。使用最近开发的FDG注射后细胞分选方法，我们发现，在细胞分辨率上，小胶质细胞表现出比神经元和星形胶质细胞更高的葡萄糖摄取。小胶质细胞葡萄糖摄取的改变是导致TREM2缺陷小鼠FDG-PET信号减少和淀粉样变性小鼠模型FDG-PET信号增加的原因。因此，相反的小胶质细胞激活状态决定了FDG摄取的差异。12例阿尔茨海默病患者和21例四重构型脑病患者保存脑区的F-18-GE-180 18-kDa转位蛋白PET(TSPO-PET)显示葡萄糖摄取与小胶质细胞活性呈正相关，表明人类大脑葡萄糖摄取也受到小胶质细胞活性的强烈影响。我们的发现表明，在神经退行性疾病患者和淀粉样变性小鼠模型中，小胶质细胞激活状态是FDG-PET信号改变的原因。因此，在进行FDG-PET时应考虑小胶质细胞的激活状态。
2-Deoxy-2-[F-18]fluoro-d-glucose positron emission tomography (FDG-PET) is widely used to study cerebral glucose metabolism. Here, we investigated whether the FDG-PET signal is directly influenced by microglial glucose uptake in mouse models and patients with neurodegenerative diseases. Using a recently developed approach for cell sorting after FDG injection, we found that, at cellular resolution, microglia displayed higher glucose uptake than neurons and astrocytes. Alterations in microglial glucose uptake were responsible for both the FDG-PET signal decrease in Trem2-deficient mice and the FDG-PET signal increase in mouse models for amyloidosis. Thus, opposite microglial activation states determine the differential FDG uptake. Consistently, 12 patients with Alzheimer's disease and 21 patients with four-repeat tauopathies also exhibited a positive association between glucose uptake and microglial activity as determined by F-18-GE-180 18-kDa translocator protein PET (TSPO-PET) in preserved brain regions, indicating that the cerebral glucose uptake in humans is also strongly influenced by microglial activity. Our findings suggest that microglia activation states are responsible for FDG- PET signal alterations in patients with neurodegenerative diseases and mouse models for amyloidosis. Microglial activation states should therefore be considered when performing FDG-PET.