Validity and Value of metabolic connectivity in AD mouse models

The goal of the current work was to analyze and validate metabolic regional network alterations in three different AD mouse models (β-amyloid and tau) by use of 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) imaging. We compared the results of FDG-µPET MC with conventional VOI-based analysis and behavioral assessment in the Morris water maze (MWM). MC proved to be an accurate and robust indicator of functional connectivity loss in AD mouse models when sample sizes ≥12 are considered. MC loss was observed throughout all brain regions in tauopathy mice, whereas β-amyloid indicated MC loss mainly in spatial learning areas and subcortical networks. This study established a methodological basis for the utilization of MC in different mouse models of AD. MC has the potential to serve as a read-out of pathological changes within neuronal networks in AD models.本研究旨在通过2-脱氧-2-[18F]氟-D-葡萄糖正电子发射断层扫描（2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography, FDG-PET）成像，分析并验证三种不同阿尔茨海默病（Alzheimer's Disease, AD）小鼠模型（β淀粉样蛋白型与tau蛋白型）的代谢区域网络异常改变。我们将FDG微型正电子发射断层扫描代谢连接的分析结果，与传统基于感兴趣体积（Volume of Interest, VOI）的分析方法以及莫里斯水迷宫（Morris water maze, MWM）行为学评估结果进行对比。当样本量≥12时，代谢连接（Metabolic Connectivity, MC）可作为阿尔茨海默病小鼠模型功能连接减退的精准且稳健的标志物。在tau蛋白病小鼠的全部脑区内均可见代谢连接减退，而β淀粉样蛋白模型的代谢连接减退主要集中于空间学习脑区与皮层下网络。本研究为代谢连接（MC）在不同阿尔茨海默病小鼠模型中的应用奠定了方法学基础，代谢连接（MC）有望作为阿尔茨海默病模型中神经元网络病理变化的检测指标。