2-Deoxy-2-[¹⁸F]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 ¹⁸F-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.

中文翻译：

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小胶质细胞激活状态驱动神经退行性疾病中的葡萄糖摄取和 FDG-PET 改变

2-脱氧-2-[ ¹⁸ F]氟-d-葡萄糖正电子发射断层扫描（FDG-PET）广泛用于研究脑葡萄糖代谢。在这里，我们研究了小鼠模型和患有神经退行性疾病的患者中 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，在细胞分辨率下，小胶质细胞比神经元和星形胶质细胞表现出更高的葡萄糖摄取量。小胶质细胞葡萄糖摄取的改变是Trem2缺陷小鼠中FDG-PET信号减少和淀粉样变性小鼠模型中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。^{一致地，通过18} F-GE-180 18-kDa 易位蛋白 PET (TSPO-PET) 在保留的大脑区域中测定，12 名阿尔茨海默氏病患者和 21 名四重复 tau蛋白病患者也表现出葡萄糖摄取与小胶质细胞活性之间的正相关性，表明人类的大脑葡萄糖摄取也受到小胶质细胞活动的强烈影响。我们的研究结果表明，小胶质细胞激活状态是神经退行性疾病患者和淀粉样变性小鼠模型中 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。