Global Energy Metabolism Deficit in Alzheimer Disease Brain.

IF 8.5 3区医学 Q1 CLINICAL NEUROLOGY

Jpad-Journal of Prevention of Alzheimers Disease Pub Date : 2024-01-01 DOI:10.14283/jpad.2023.91

V Patel, J Mill, O C Okonkwo, S Salamat, L Li, T Raife

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Abstract

Background: The understanding of Alzheimer's disease (AD) has been dominated by the amyloid hypothesis. However, therapies targeting beta-amyloid have largely failed, generating interest in other potential pathogenic factors including energy metabolism.

Objectives: To interrogate canonical energy metabolism pathways from human prefrontal cortical tissue samples obtained from necropsy comparing AD and control.

Design, setting, and participants: Postmortem pre-frontal cortical tissue from 10 subjects histologically diagnosed with AD and 10 control (CTRL) subjects was subjected to untargeted metabolomics to interrogate energy metabolism pathways. The samples were matched by age, sex, and post-mortem interval. Metabolite Measurements: Untargeted metabolomics analyses were via Metabolon®.

Results: Glucose-derived energy metabolites in the glycolytic and pentose phosphate pathway and the ketone body β-hydroxybutyrate were uniformly decreased in AD brain vs. CTRL brain.

Conclusion: This pilot study aimed to identify energy metabolism abnormalities using untargeted brain metabolomics in two independent subject cohorts. Our study revealed a pattern of global energy deficit in AD brain, supporting a growing body of evidence of deficient energy metabolism in AD.

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阿尔茨海默氏症大脑中的全球能量代谢缺陷。

背景：人们对阿尔茨海默病（AD）的认识一直以淀粉样蛋白假说为主。然而，针对β-淀粉样蛋白的疗法大多以失败告终，这引起了人们对包括能量代谢在内的其他潜在致病因素的兴趣：目的：从尸体解剖获得的人类前额叶皮质组织样本中研究典型的能量代谢途径，并对AD和对照组进行比较：对10名组织学诊断为AD的受试者和10名对照组（CTRL）受试者的死后前额叶皮质组织进行非靶向代谢组学研究，以探究能量代谢途径。样本按年龄、性别和死后间隔时间进行匹配。代谢物测量：通过 Metabolon® 进行非靶向代谢组学分析：结果：与CTRL脑相比，AD脑中糖酵解和磷酸戊糖途径中的葡萄糖源能量代谢物以及酮体β-羟丁酸均一致减少：这项试验性研究旨在利用非靶向脑代谢组学确定两个独立受试者队列中的能量代谢异常。我们的研究揭示了AD大脑的整体能量缺乏模式，支持了越来越多关于AD能量代谢不足的证据。

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来源期刊

Jpad-Journal of Prevention of Alzheimers Disease CLINICAL NEUROLOGY-

自引率

7.80%

发文量

期刊介绍： The JPAD « Journal of Prevention of Alzheimer’Disease » will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including : neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes. JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.