Background:White matter energy supply to oligodendrocytes and the axonal compartment is crucial for normal axonal function. Although gray matter glucose hypometabolism is extensively reported in Alzheimer’s disease (AD), glucose and ketones, the brain’s two main fuels, are rarely quantified in white matter in AD. Objective:Using a dual-tracer PET method combined with a fascicle-specific diffusion MRI approach, robust to white matter hyper intensities and crossing fibers, we aimed to quantify both glucose and ketone metabolism in specific white matter fascicles associated with mild cognitive impairment (MCI; n = 51) and AD (n = 13) compared to cognitively healthy age-matched controls (Controls; n = 14). Methods:Eight white matter fascicles of the limbic lobe and corpus callosum were extracted and analyzed into fascicle profiles of five sections. Glucose (18F-fluorodeoxyglucose) and ketone (11C-acetoacetate) uptake rates, corrected for partial volume effect, were calculated along each fascicle. Results:The only fascicle with significantly lower glucose uptake in AD compared to Controls was the left posterior cingulate segment of the cingulum (–22%; p = 0.016). Non-significantly lower glucose uptake in this fascicle was also observed in MCI. In contrast to glucose, ketone uptake was either unchanged or higher in sections of the fornix and parahippocampal segment of the cingulum in AD. Conclusion:To our knowledge, this is the first report of brain fuel uptake calculated along white matter fascicles in humans. Energetic deterioration in white matter in AD appears to be specific to glucose and occurs first in the posterior cingulum.

中文翻译：

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阿尔茨海默氏病白质能量供应中的束状和葡萄糖特异性恶化。

背景：少突胶质细胞和轴突区室的白质能量供应对于正常的轴突功能至关重要。尽管在阿尔茨海默氏病（AD）中广泛报道了灰质葡萄糖代谢不足，但大脑中的两种主要燃料葡萄糖和酮很少在AD的白质中定量。目的：使用双示踪PET方法结合专一的束状弥散MRI方法，对白质过高强度和交叉纤维具有鲁棒性，我们旨在量化与轻度认知障碍（MCI）相关的特定白质束中葡萄糖和酮代谢； n = 51）和AD（n = 13），与认知健康的年龄匹配对照组（对照组； n = 14）相比。方法：提取角膜缘和体的八个白质束，并将其分析为五个部分的束轮廓。沿每个分册计算校正了部分体积效应的葡萄糖（18F-氟脱氧葡萄糖）和酮（11C-乙酰乙酸酯）的摄取率。结果：与对照组相比，AD中唯一葡萄糖摄取明显降低的纤维束是扣带的左扣带回段（–22％； p = 0.016）。在MCI中也观察到该分册中葡萄糖的摄取没有明显降低。与葡萄糖相反，AD中扣带的穹and和海马旁部分的酮摄入量不变或更高。结论：据我们所知，这是人类第一个根据白质束计算出的脑燃料摄入量的报告。AD中白质的能量退化似乎是葡萄糖特有的，首先发生在后扣带。