Damaged mitochondria may be one of the earliest manifestations of Alzheimer's disease. Because oxidative phosphorylation is a primary source of neuronal energy, unlike glycolysis-dependent energy production in inflamed glia, mitochondrial respiration could provide a selective biomarker of neuronal deterioration in Alzheimer's disease. Here we used a recently developed positron emission tomography (PET) probe targeting mitochondrial complex I (MC-I), 18F-BCPP-EF, to non-invasively visualize mitochondrial abnormalities in the brains of tau transgenic mice (rTg4510). Tauopathy and neuroinflammation were visualized by PET using a tau probe 11C-PBB3 and a translocator protein probe, 18F-FEBMP, respectively. A marked reduction in 18F-BCPP-EF uptake was observed in hippocampal and forebrain regions of tau transgenic mice, colocalizing with regions of tauopathy, neuronal damage, and neuroinflammation. MC-I signals were highly correlated with atrophy assayed by magnetic resonance imaging, but negatively associated with inflammatory signals, indicating that neuronal metabolic signals measured by MC-I PET were robust to inflammatory interference. MC-I may be a useful imaging biomarker to detect neuronal damage and metabolic changes with minimal interference from concomitant glial hypermetabolism.

中文翻译：

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tau 蛋白病变小鼠模型中线粒体异常的体内 PET 成像

受损的线粒体可能是阿尔茨海默病的最早表现之一。由于氧化磷酸化是神经元能量的主要来源，与发炎神经胶质中依赖糖酵解的能量产生不同，线粒体呼吸可以提供阿尔茨海默病神经元退化的选择性生物标志物。在这里，我们使用最近开发的正电子发射断层扫描 (PET) 探针靶向线粒体复合体 I (MC-I)、18F-BCPP-EF，以非侵入性方式可视化 tau 转基因小鼠 (rTg4510) 大脑中的线粒体异常。分别使用 tau 探针 11C-PBB3 和易位蛋白探针 18F-FEBMP 通过 PET 观察 Tau 蛋白病变和神经炎症。在 tau 转基因小鼠的海马和前脑区域观察到 18F-BCPP-EF 摄取显着减少，与 tau 蛋白病变、神经元损伤和神经炎症区域共定位。MC-I 信号与磁共振成像测定的萎缩高度相关，但与炎症信号呈负相关，表明 MC-I PET 测量的神经元代谢信号对炎症干扰具有鲁棒性。MC-I 可能是一种有用的成像生物标志物，用于检测神经元损伤和代谢变化，同时将伴随的神经胶质高代谢的干扰降至最低。