Lower GLUT1 and unchanged MCT1 in Alzheimer's disease cerebrovasculature.

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Manon Leclerc, Cyntia Tremblay, Philippe Bourassa, Julie A Schneider, David A Bennett, Frédéric Calon
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Abstract

The brain is a highly demanding organ, utilizing mainly glucose but also ketone bodies as sources of energy. Glucose transporter-1 (GLUT1) and monocarboxylates transporter-1 (MCT1) respectively transport glucose and ketone bodies across the blood-brain barrier. While reduced glucose uptake by the brain is one of the earliest signs of Alzheimer's disease (AD), no change in the uptake of ketone bodies has been evidenced yet. To probe for changes in GLUT1 and MCT1, we performed Western immunoblotting in microvessel extracts from the parietal cortex of 60 participants of the Religious Orders Study. Participants clinically diagnosed with AD had lower cerebrovascular levels of GLUT1, whereas MCT1 remained unchanged. GLUT1 reduction was associated with lower cognitive scores. No such association was found for MCT1. GLUT1 was inversely correlated with neuritic plaques and cerebrovascular β-secretase-derived fragment levels. No other significant associations were found between both transporters, markers of Aβ and tau pathologies, sex, age at death or apolipoprotein-ε4 genotype. These results suggest that, while a deficit of GLUT1 may underlie the reduced transport of glucose to the brain in AD, no such impairment occurs for MCT1. This study thus supports the exploration of ketone bodies as an alternative energy source for the aging brain.

阿尔茨海默氏症脑血管中的 GLUT1 降低,MCT1 不变。
大脑是一个需要大量能量的器官,主要利用葡萄糖,但也利用酮体作为能量来源。葡萄糖转运体-1(GLUT1)和单羧酸盐转运体-1(MCT1)分别通过血脑屏障转运葡萄糖和酮体。大脑对葡萄糖的吸收减少是阿尔茨海默病(AD)最早出现的症状之一,但目前还没有证据表明酮体的吸收发生了变化。为了探究 GLUT1 和 MCT1 的变化,我们对 60 名宗教团体研究参与者顶叶皮层的微血管提取物进行了 Western 免疫印迹分析。临床诊断为AD的参与者脑血管中的GLUT1水平较低,而MCT1则保持不变。GLUT1 的降低与认知评分的降低有关。而 MCT1 则没有发现这种关联。GLUT1与神经斑块和脑血管β-分泌酶衍生片段水平成反比。在这两种转运体、Aβ和tau病理标记物、性别、死亡年龄或载脂蛋白-ε4基因型之间没有发现其他重要关联。这些结果表明,虽然GLUT1的缺失可能是导致AD患者大脑葡萄糖转运减少的原因,但MCT1却没有出现这种障碍。因此,这项研究支持探索将酮体作为衰老大脑的替代能源。
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来源期刊
Journal of Cerebral Blood Flow and Metabolism
Journal of Cerebral Blood Flow and Metabolism 医学-内分泌学与代谢
CiteScore
12.00
自引率
4.80%
发文量
300
审稿时长
3 months
期刊介绍: JCBFM is the official journal of the International Society for Cerebral Blood Flow & Metabolism, which is committed to publishing high quality, independently peer-reviewed research and review material. JCBFM stands at the interface between basic and clinical neurovascular research, and features timely and relevant research highlighting experimental, theoretical, and clinical aspects of brain circulation, metabolism and imaging. The journal is relevant to any physician or scientist with an interest in brain function, cerebrovascular disease, cerebral vascular regulation and brain metabolism, including neurologists, neurochemists, physiologists, pharmacologists, anesthesiologists, neuroradiologists, neurosurgeons, neuropathologists and neuroscientists.
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