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NMR Analysis of the Correlation of Metabolic Changes in Blood and Cerebrospinal Fluid in Alzheimer Model Male and Female Mice
bioRxiv - Neuroscience Pub Date : 2020-05-29 , DOI: 10.1101/2020.05.26.116525
Filip Stojanovic , Mariam Taktek , Nam Huan Khieu , Junzhou Huang , Susan Jiang , Kerry Rennie , Balu Chakravarthy , Will J. Costain , Miroslava Cuperlovic-Culf

The development of effective therapies as well as early, molecular diagnosis of Alzheimers disease is impeded by the lack of understanding of the underlying pathological mechanisms. Metabolomics studies of body fluids as well as brain tissues have shown major changes in metabolic profiles of Alzheimers patients. However, with analysis performed at the late stages of the disease it is not possible to distinguish causes and consequence. The mouse model APP/PS1 expresses a mutant amyloid precursor protein resulting in early Amyloid beta accumulation as well as many resulting physiological changes including changes in metabolic profile and metabolism. Analysis of metabolic profile of cerebrospinal fluid (CSF) and blood of APP/PS1 mouse model can provide information about metabolic changes in these body fluids caused by Amyloid beta accumulation. Using our novel method for analysis of correlation and mathematical ranking of significant correlations between metabolites in CSF and blood, we have explored changes in metabolite correlation and connectedness in APP/PS1 and wild type mice. Metabolites concentration and correlation changes in CSF, blood and across the blood brain barrier determined in this work are affected by the production of plaque. Metabolite changes observed in the APP/PS1 mouse model are the response to the mutation causing plaque formation, not the cause for the plaque suggesting that they are less relevant in the context of early treatment and prevention then the metabolic changes observed only in humans.

中文翻译:

阿尔茨海默病模型雄性和雌性小鼠血液和脑脊液代谢变化相关性的NMR分析

由于缺乏对潜在病理机制的了解,阻碍了阿尔茨海默氏病的有效疗法以及早期分子诊断的发展。体液和脑组织的代谢组学研究表明,阿尔茨海默氏症患者的代谢谱发生了重大变化。但是,通过在疾病晚期进行分析,无法区分原因和后果。小鼠模型APP / PS1表达突变淀粉样前体蛋白,导致早期淀粉样β积累以及许多由此引起的生理变化,包括代谢谱和代谢变化。分析APP / PS1小鼠模型的脑脊液(CSF)和血液的代谢谱可提供有关这些淀粉样β积累引起的这些体液代谢变化的信息。使用我们新颖的方法分析脑脊液和血液中代谢物之间的相关性和相关性的数学排序,我们探索了APP / PS1和野生型小鼠中代谢物相关性和连通性的变化。在这项工作中确定的脑脊液,血液和整个血脑屏障中的代谢物浓度和相关性变化会受到斑块产生的影响。在APP / PS1小鼠模型中观察到的代谢物变化是对引起斑块形成的突变的反应,而不是斑块的原因,表明它们在早期治疗和预防中的相关性较仅在人类中观察到的代谢变化低。我们已经研究了APP / PS1和野生型小鼠中代谢物相关性和连通性的变化。在这项工作中确定的脑脊液,血液和整个血脑屏障中的代谢物浓度和相关性变化会受到斑块产生的影响。在APP / PS1小鼠模型中观察到的代谢物变化是对引起斑块形成的突变的反应,而不是斑块的原因,表明它们在早期治疗和预防中的相关性较仅在人类中观察到的代谢变化低。我们已经探索了APP / PS1和野生型小鼠中代谢物相关性和连通性的变化。在这项工作中确定的脑脊液,血液和整个血脑屏障中代谢物的浓度和相关性变化会受到斑块产生的影响。在APP / PS1小鼠模型中观察到的代谢物变化是对引起斑块形成的突变的反应,而不是斑块的原因,表明它们在早期治疗和预防中的相关性较仅在人类中观察到的代谢变化低。
更新日期:2020-05-29
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