Metabolomic Analysis Identifies Alterations of Amino Acid Metabolome Signatures in the Postmortem Brain of Alzheimer's Disease
Metabolomic Analysis Identifies Alterations of Amino Acid Metabolome Signatures in the Postmortem Brain of Alzheimer's Disease
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DOI：
10.5607/en.2019.28.3.376
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发表时间：
2019-06-01
影响因子：
2.4
通讯作者：
Lee, Jeongae
中科院分区：
文献类型：
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作者：
Kim, Yoon Hwan;Shim, Hyun Soo;Lee, Jeongae
尽管在过去的几十年里神经科学研究取得了重大进展，但AD的确切原因尚未完全了解。代谢假说以及淀粉样蛋白和tau假说已被提出与AD发病机制相关。为了鉴定来自散发性All患者和对照受试者的死后脑的代谢组特征，我们进行了超高效液相色谱-线性离子阱-轨道阱质谱仪（UPLC-LTQ-Orbitrap-MS）。我们的研究不仅确定了新的代谢组特征，还验证了以前已知的大脑代谢组特征。分析数据的统计建模和结构分配的验证发现了与AD发病机制相关的代谢生物标志物。有趣的是，AD患者死后脑组织中的下牛磺酸、肌醇和氧代脯氨酸水平显着升高，而谷氨酸和N-乙酰基-天冬氨酸水平下降。此外，AD患者皮质醇等神经甾体激素水平显著升高。总之，我们的数据表明，受损的氨基酸代谢与AD的发病机制和改变的氨基酸签名可以是有用的诊断生物标志物的所有。因此，调节氨基酸代谢可能是治疗AD的一种可能的治疗方法。
Despite significant advances in neuroscience research over the past several decades, the exact cause of AD has not yet fully understood. The metabolic hypothesis as well as the amyloid and tau hypotheses have been proposed to be associated with AD pathogenesis. In order to identify metabolome signatures from the postmortem brains of sporadic All patients and control subjects, we performed ultra performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer (UPLC-LTQ-Orbitrap-MS). Not only our study identified new metabolome signatures but also verified previously known metabolome profiles in the brain. Statistical modeling of the analytical data and validation of the structural assignments discovered metabolic biomarkers associated with the AD pathogenesis. Interestingly, hypotaurin, myo-inositol and oxo-proline levels were markedly elevated in AD while glutamate and N-acetyl-aspartate were decreased in the postmortem brain tissue of AD patients. In addition, neurosteroid level such as cortisol was significantly increased in AD. Together, our data indicate that impaired amino acid metabolism is associated with AD pathogenesis and the altered amino acid signatures can be useful diagnostic biomarkers of All. Thus, modulation of amino acid metabolism may be a possible therapeutic approach to treat AD.